To define specifications and procedures for all materials and method of manufactured and control. To ensure that all personal concern with manufacture know what to do and when to do it.

1. DOCUMENTATION IN PHARMACEUTICAL INDUSTRY :
WORKING INSTRUCTIONS AND RECORD FORMATS
Presented by:
Pv. Sai Viswanath
M.pharm
Department of pharmaceutical analysis
Gokaraju Rangaraju College of Pharmacy
Under the Guidance of
Dr G Ashok
Associate Professor
Gokaraju Rangaraju College of Pharmacy

2. WHAT IS DOCUMENTATION?
• Document is a paper providing information especially of an official or legal nature, written report or record.
• Documentation is an integral part of good manufacturing practices.
• 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.
• The main purpose of documentation is to define procedures in written to the pharmaceutical manufacturer
so as to minimize the errors, misinterpretations due to oral or casually written communication and to allow
the tracing of historical batches which eventually leads to the quality of the product. Documentation is an
integral part of good manufacturing practices. It defines a system of information and control so that risks so
inherent in misinterpretation and/or error in oral communication are minimized.
• It consequently strengthens the quality and its consistency of all goods and services as those responsible for
the specific operations have clear unambiguous instructions to follow including active drug substances is
legally mandatory. The purpose of this work is to specify the GMP requirements on documentation within
pharmaceutical industry.

3. OBJECTIVES OF DOCUMENTS
• To define specifications and procedures for all materials and method of manufactured and control.
• To ensure that all personal concern 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 realize a batch
of drug for sale.
• To ensure the existence of documented evidence , trace ability and adult trail that will permit investigation.

4. SCOPE
• Building and Premises: Installation, Validation, Cleaning and Maintenance.
• Personnel: Training, Hygiene.
• Equipment: Installation, Calibration, Validation, Maintenance and Cleaning
• Materials : Specifications, Testing, Ware housing, Use Rejection/ Disposal
• Processing: Individual steps in the process of manufacturing include controls
• Finished goods : Specifications, Testing, Storage, Distribution and Rejection and disposal.

5. MASTER FORMULA RECORD
• Written procedure that give the complete description of all aspects of manufacture, packing and control with
an inspection to ensure purity, identity, quality and strength of each dosage unit through its shelf life.
Includes all the materials used in any batch manufacturing and step by step process of manufacturing.
• Definition “A document or set of documents specifying the starting materials with their quantities and the
packaging materials, together with a description of the procedures and precautions required to produce a
specified quantity of a finished product as well as the processing instructions, including the in-process
controls.” There shall be Master Formula records relating to all manufacturing procedures for each product
and batch size to be manufactured. These shall be prepared and endorsed by the competent technical staff
i.e., head of production and quality control. MFR plays an important in consistency for each batch
manufacturing.
• The master formula must include:
1) The name of the product together with product reference code relating to its specifications.
2) The patent or proprietary name of the product along with the generic name, a description of dosage form,
strength, composition of the product and batch size.

6. 3) A statement of the processing location and the principal equipment to be used.
4) Name , quantity and reference number of all starting materials to be used.
5) A statement of expected final yield with the acceptable limits and of relevant intermediate yields, where
applicable.
6) The methods or reference of the methods to be used for preparing the critical equipment including cleaning,
assembling, calibrating, sterilizing.
7) Detailed stepwise processing instructions and the time taken for each step.
1. Product Details: Name, logo and address of the manufacturing company.
2. Dosage form name.
3. Brand name.
4. Generic name.
5. Product code
6. Label claim of all ingredients
7. Product description
8. Batch size

7. • Master production and control records:
• Detailed written instructions including all operations starting from dispensing of raw materials till finishing of
bulk products and packaging operation of the particular product.
• It includes batch size, date of manufacture and full signature by 1st person and further independently checked,
dated and signed by 2nd person.
• Preparation of master formula :
• Master formula can be prepared by competent technical staff.
• It should be reviewed by the head of production, QC department and R & D department.

8. BATCH MANUFACTURING RECORD
• The batch manufacturing record (BMR) is a document containing the instructions that must be followed
when manufacturing medication. It includes information like product name, weight and count of each
component in the medication, a list of all processes and procedures to follow, and the expected yield of each
batch. Before any processing begins, a check should be performed and recorded to ensure that the
equipment and workstation are clear of previous products, documents, or materials not required for the
planned process and that the equipment is clean and suitable for use. These records should be numbered
with a unique batch or identification number and dated and signed when issued. The “Batch Manufacturing
Record” is the necessary quality and GMP documentation for tracing the complete cycle of manufacturing
batch.
• Responsibility:
• Primary: Officer–QA / Officer–QC/ Officer-Production
• Secondary: Manager-QA/ Manager- QC/ Manager- Production Pharmaceutical Quality Assurance.

9.  In-processing and laboratory control results
 A statement of the actual yield and as percentage of theoretical yield
at appropriate phases of processing.
 Signed authorization if there is any deviation from the master formula
record and/ or batch manufacturing process.
 Complete labeling control record including specimens or copies of all
labeling used.
 Description drug product containers and closures.
 Any sampling performed.
 Identification of the persons performing and directly supervising or
checking each significant step in the operations.
 Reconciliation of materials received , used, rejected and/or destroyed.
• A decision for the release or rejection of the batch, with the date and
signature of the person responsible for the decision.
• Production and quality control records should be reviewed as part of
the approval process of batch release.

10. QUALITY AUDIT
• “A systematic and independent examination to determine whether quality activities and related results
comply with planned arrangements, and whether these arrangements are implemented effectively and are
suitable to achieve objectives”.
• Quality audit means a systemic examination of a quality system.
• Quality audits are typically examined at defined intervals.
• Types of audit :
1) Internal audit
2) External audit
3) Regulatory audit

11. AUDIT ACTIVITIES

Initiating the audit

Preparing audit activities

Conducting audit activities

Preparing and distributing audit activities

Completing the audit

Conducting audit follow-up
(If specified in audit plan)

12. AUDIT PLAN
• Required for effective audit at low cost.
• A comprehensive list of the specific audit procedures that the audit team needs to perform to gather sufficient
appropriate evidence on which to base their opinion on the financial statements.
• Audit planning is carried out before start of audit.
• When planning the engagement, the auditor needs to develop and document a plan that describes the
procedures to be performed to assess the risk of material misstatement at the financial statement and assertion
level.
• The auditor must then carefully plan the nature, timing and extent of control tests and substantive tests that
are designed to mitigate these risks to an acceptable level.
• OBJECTIVES OF QUALITY AUDIT:
 To determine conformity or non-conformity of the quality system elements with specified requirements.
 To determine the effectiveness of the implemented system in meeting specific quality objectives.
 To afford an opportunity to improve the quality system.

13. AUDIT DOCUMENTATION:
1.Written record of the basis for the auditor’s conclusion that
provides the support for the auditor’s representations, whether
those representations are contained in the auditor’s report or
otherwise.
2.It includes records of the planning and performance of the work,
the procedures performed, evidence obtained.
AUDIT REPORT :
1. Financial records and accounts of the company.
2. The audit reporting is the communication of audit conclusions
after having carried out the audit process in accordance with the
audit plan.
3. Signed written document which presents the purpose, scope
and results of the audit.

14. SPECIFICATIONS
• Authorized and dated specifications for starting materials, packaging materials, finished products,
intermediates and bulk products.
• Approved and maintained by the QC department.
• Periodic review is necessary.
• In India, D&C act requires the drugs to comply with standards as laid down in the 2nd schedule.
In case of pharmaceutical products, we need specification for:
1). Active and inactive starting materials.
2). Primary, printed, and other packing materials.
3). Intermediate and bulk products.
4). Finished pharmaceutical products.

15. • Specification for starting & packaging material
Specifications for starting, primary and printed packaging materials should include, if applicable:
1). A description of the materials. Including
(a) The designated name and internal code reference.
(b) The reference, if any, to a pharmacopeial monograph.
(c) Qualities and quantitative requirement with acceptance limit.
2 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) Direction for sampling and testing, or a reference to procedures.
(d) Storage conditions and precautions.
(e) The maximum period of storage before re-examination.
• Packaging material should conform to specifications, and should be compatible with the material and/or with
the drug product it contains. The material should be examined for compliance with the specification, and for
defects as well as for the correctness of identity markings.
• Specification for intermediate & bulk product
Specifications for intermediate and bulk products should be available. The specifications should be similar to
specifications for starting materials or for finished products, as appropriate.

16. PROTOCOLS
1. Serial number of the Batch Manufacturing Record.
2. Name of the product.
3. Reference to Master Formula Record.
4. Batch/Lot number.
5. Batch/Lot size.
6. Date of commencement of manufacture and date of completion of manufacture.
7. Date of manufacture and assigned date of expiry.
8. Date of each step in manufacturing.
9. Names of all ingredients with the grade given by the quality control department.
10. Quality of all ingredients.

17. DISTRUBUTION RECORD
• Distribution records Written procedures shall be established and followed, describing the distribution of
drug products Include:
• A procedure where by the oldest approved stock of a drug product is distributed first.
• A system by which the distribution of each lot of drug product can be readily determined to facilitate its
recall if necessary.
• Distribution records must be constructed and procedures established to facilitate recall of defective product.
• All records should be indexed by either the manufacturing batch-lot number of the packaging control
number as a means of accountability.
• Distribution procedure: It shall include the following: -
• A procedure whereby the oldest approved stock of a drug product is distributed first. Deviation from this
requirement is permitted if such deviation is temporary and appropriate.
• A system by which the distribution of each lot of drug product can be readily Determined to facilitate its
recall if necessary.

18. • It shall contains:
• Name and strength of the product.
• Description of dosage form.
• Name and address of the consigner.
• Date and quantity shipped.
• Lot and control number of the drug.
• WHO guidelines for distribution records:
• Written instruments and records should be available.
• Procedure should be established and maintained.
• The title, name and purpose of each document should be clearly stated.
• All documents should be completed, approved ,signed ad dated by an appropriate authorized persons.
• In the case of temperature-sensitivity pharmaceutical products, records of investigations and actions should be
retained for at least one year after the expiry date of the product.

19. ELECTRONIC DATA HANDLING
• Electronic data handling is also known as EDH, a frequently used term for automatic information
processing. It uses the computers to collect, manipulate, record, classification and to summarize data. EDH
meaning can be described as the processing of data using electronic means such as computers, calculators,
servers and other similar electronic data processing equipment. A computer is the best example of an EDH
system, where total data is stored.
• FDA has provided a tool which makes data more secure, accurate, long-lasting and authenticate. This tool is
known as ALCOA. Were,
• A- ATTRIBUTABLE
• L- LEGIBLE
• C- CONTEMPORANEOUS
• O- ORIGINAL
• A- ACCURATE

20. • Electronic records in an automation system & are easier to keep than manual records. Records generated and
maintained by the automation system include:
• Recipe handling.
• System configuration.
• Device calibration.
• Operator input.
• Audit trail.
• Alarm and event history.
• Trends and batch records.
• API first in/ first come.

21. REFFERENCES
1. Guide to Master Formulae WHO/FWC/IVB/QSS/VQR 2011 World Health Organization Pg.No1-14 & 49
(https://www.who.int/immunization_standards/vaccine_quality/guide_to_master_formulae_final_2012.pdf)
2. Drug Master Files Guidelines, Center for Drug Evaluation and Research Food and Drug Administration,
Department of Health and Human Services September 1989
(https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm122886.html)
3. A Textbook of Pharmaceutical Quality assurance by Mr. Sanjay A. Nagdev, Mr. Mayur R. Bhurat, Dr. Md.
Rageeb Md. Usman Dr. Krishna R. Gupta, Dr. Upendra B. Gandagule
4. Puneet Dhamija et.al, 2015 Only generics (drugs/names): Is India ready? Indian Journal Endocrinology
Metabolism (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566332/)
5. Overview on Hatch Waxman act, The Innovative Pharmaceutical association South Africa (IPASA)

22. THANK YOU