COMPLAINT HANDLING IN PHARMACEUTICAL COMPANIES,PRODUCT RECALL,RETENTION RECORDS, DISTRIBUTION RECORDS.prepared by s.susena,m.pharmacy pharmaceutical analysis&QA,ssj college of pharmacy

1. PREPARED BY
S.SUSENA,
SSJ COLLEGE OF PHARMACY,
M.PHARMACY(P.ANALYSIS&QA)
DOCUMENTATION RELATING TO PRODUCT
DEVELOPMENT,
STANDARD OPERATING PROCEDURES,
CLEANING METHODS,
QUALITY CONTROL DOCUMENTATION

2. DEFINITION
Documentation is a process that involves the systematic interaction of people, events
and documents to create the records of the organization / corporation. There is saying in the
pharmaceutical industry- ‘if it hasn’t been documented, then it hasn’t happened!’ It acts as a
proactive vehicle for communication.
Document :- A piece of written, typed, printed/electronic matter that provides
information/evidence.
PRINCIPLES
 Good documentation constitutes an essential part of the quality assurance system.
 Clearly written documentation prevents errors from spoken communication and permits
tracing of batch history.
 “Your documentation is an advertisement for your work”.
OBJECTIVES
 To define all materials specifications.
 To ensure all personal of manufacture and control department know what to do and when to
do.
 To provide information during investigation, if a batch is suspected to have defect(s).

3. ESSENTIAL CHARACTERISTICS
 The document directing the manufacturing event fulfills current regulatory
commitments.
 The directive document is appropriate for the task to be performed.
 The data is accurate and legible.
 The data is authentic.
 The data collected fulfills specifications.
 The original data and the original documents (manufacturing record) are
retrievable for review or audit.
REQUIREMENTS FOR A GOOD DOCUMENTATION
For effective use of documents, they should be designed and prepared
with utmost care. Each document shall:
 Have a clear title.
 Have an identification number.
 Be approved by authorized person.
 Have the date of issue.

4. INCEPTION
DESIGN
PREPARATION
APPROVAL CREATION OF NEW DOC.
AUTHORIZATION
COMMUNICATION
TRAINING
IMPLEMENTATION
PERIODIC REVIEW
REVISION
REVISED OBSOLESCENCE
DOCUMENT
WITHDRAWAL
ARCHIVING

5. TYPES OF DOCUMENTS : There are three types of Documents -
1. Commitment Documents: Relationship between industry and the regulatory
authorities.
Ex: New Drug Applications (NDAs), Drug Master Files (DMFs) etc.
 These present corporate goals, expectations and standard of practice.
 Describes what to do . . . . . . ???
 It organizes the work in a manner that assures efficient and effective work flow.
 Written to lead and guide the work and workers.
 To be used as active documents that are consulted and followed routinely.
 Deviations from regulatory submissions can have significant impact on product
quality.
 Any deviation must be documented and managed.

6.  New Drug Applications (NDAs):- The New Drug Application (NDA) is the vehicle
in the United States through which drug sponsors formally propose that the FDA
approve a new pharmaceutical for sale and marketing. The goals of the NDA are
to provide enough information to permit FDA reviewers to establish the following:
 Is the drug safe and effective in its proposed use(s)
 Is the drug‟s proposed labeling (package insert) appropriate
 Are the methods used in manufacturing (Good Manufacturing Practice, GMP)
the drug and the controls used to maintain the drug‟s quality adequate to
preserve the drug‟s identity, strength, quality, and purity?
 Drug Master Files (DMFs):- Drug Master File or DMF is a document prepared by
a pharmaceutical manufacturer and submitted solely at its discretion to the
appropriate regulatory authority in the intended drug market. However, the
document provides the regulatory authority with confidential, detailed information
about facilities, processes, or articles used in the
manufacturing, processing, packaging, and storing of one or more human drugs.
Drug Master File (DMF) is a document containing complete information on
an Active Pharmaceutical Ingredient (API) or finished drug dosage form. The
DMF contains factual and complete information on a drug product‟s
chemistry, manufacture, stability, purity, impurity profile, packaging, and the
cGMP status of any human drug product.

7. 2. Directive Documents: Relationship between the Management and Employees.
Ex: Specifications, Standard Test Processes (STPs), Standard Operating
Procedures (SOPs), Medicinal Product Records (MPRs) etc.
 They establish the standards for resources, processing, products & quality
system.
 It facilitates the development, production, testing and distribution of a product
in a defined manner.
 Describe how to do . . . . . . ???
 There are several types of directive documents which are determined by the
specific, functional purpose of the document in the document system.
 Specifications:- A document specification contains several parts: a description
of the audience(s) for the document, a detailed outline giving the structure
and contents of the document, and a work plan showing who is responsible
for each part of the document and what the deadlines are for completing each
task.

8. There are three purposes for document specifications:
 Economy of Effort: First, document specifications are used to help you reduce
the amount you have to write.
E.g.- When you want to write a major report, first you prepare a draft for it, then
revise this draft & then make a document out of it.
You can often reduce this work load if you write a detailed document
specification instead. A document specification is much easier to
create, change, revise, and add to than a draft is.
 Work planning: The second major function of a document specification is work
planning. This can mean either budgeting your own time, or distributing the
work among many people. You should bear three things in mind in dividing the
work: even work load, respective areas of expertise, and getting things done in
order that you need them.
 Writing Organization: The third major function is organization of the report itself.

9.  Standard Operating Procedures (SOPs):- A Standard Operating Procedure
(SOP) is a set of written instructions that guide employees in their areas of
responsibility. The development and use of SOPs are an integral part of a
successful quality system as it provides individuals with the information to
perform a job properly, and facilitates consistency in the quality and integrity
of a product or end-result. The term “SOP” may not always be appropriate
and terms such as protocols, instructions, worksheets, and laboratory
operating procedures may also be used.
3. Record Documents : Relationship between the Employees and the Work they
perform.
Ex: Protocols, Batch Production Records (BPRs), Log Books, Calibration Records
etc.
 Protocol:- Protocols are written records clearly defining the objectives and
methods that will be used for the validation programs. An important part of
the protocol is the description of the testing method including who will test
the system, how they will test it and what data is to be collected and
reported.
Computerized system protocols often include three distinct stages:
Installation Qualification(IQ), Operational Qualification (OQ), and
Performance Qualification (PQ).

10. STANDARD OPERATING PROCEDURES
(SOP)INTRODUCTION
SOPs document a process in the form of „who‟ „what‟ „when‟ and ‟how‟. They
define how a task is to be performed, to achieve a specified outcome and standardize
the way it is to be performed so as to minimize variation.
BENEFITS
 SOPs are used as checklists by inspectors when auditing procedure.
 Ultimately the benefits of valid SOP are reduce work effort, along with improved
data comparability and legal defensibility.
 A collection of well written SOPs and supporting documents can therefore act as
critical foundation for process improvement and organization efficiency.
TYPES
1. Administrative Type:- It covers permissions and access control to specific data
or areas of a facility. Administrative SOPs can be written for wide variety of
activities, for example reviewing documentation such as contracts, QA project
plans and quality management plans; inspecting (auditing); determining
organizational training needs.

11. 2. Technical Type:- The second type is the technical type, such as operation of the
tablet compression machine, i.e. operations being performed by technicians in
the production area. Sometimes companies also use more specific types of
functional document called work instruction to provide details on how one person
accomplishes his or her job. A work instruction in any case is always related to
technical procedures rather than administrative ones.
CONTENTS OF SOPS
An SOP includes:-
 A list of materials and components required for processing.
 Full description of reagents, components or handling that must be performed
before process initiation.
 A list of equipment required and its relevant features that may include
capacities, precision, and compatibilities and limitations.
 A stepwise description of the processing event.
 Process control parameters with testing limits or acceptance criteria.

12. LIFE CYCLE OF SOPs
CREATE/EDIT
REVIEW
APPROVE
PUBLISH
DISTRIBUTE
ARCHIVE

13. GUIDE FORMAT FOR SOP
This SOP is for oral liquid filling machine.
_______________________________________________________
Name of Company _______________________________________
Address ________________________________________________
SOP FOR CLEANING OF LIQUID ORAL FILLING MACHINE
SOP NO. …………………. Effective from ……………….. (Date)
________________________________________________________________________
Prepared by checked by Responsibility
Section Supervisor
________________________________________________________________________
Approved by
In-charge In-charge
Production Quality control
________________________________________________________________________
1. Drain out holding tank of left overs, if any.
2. Fill the holding tank with water up to a height of ________ cm washing the internal surfaces and switch on filling machine. Run the machine till the water is removed from
holding tank (as much as is possible).
3. Now open the drain valve of holding tank.
4. Disassemble nozzles and washer.
5. Remove tubing.
6. Clean all parts with jet of water for _______ minutes.
7. Soak parts and flexible tubings in antiseptic solution for 30 min. (0.5% cetrimide solution can be used for this purpose).
8. Wash these parts & tubings in running water.
9. Soak these in previously boiled & hot purified water.
10. If steam is available subject the parts to live steam. If steam is not available, use 70% Isopropyl alcohol and allow to dry.
11. Clean the flexible tubing in the similar way.
12. Cover ends of clean tubing with polyethylene sheets.
13. Clean the holding tank with previously boiled & hot purified water. If steam is not available, treat the holding tank with sodium hypochlorite solution (0.1%).
14. Assemble the equipment.
15. Label the equipment with status label e.g. “Ready for use”.
__________________________________________________________________________

14. SOP DOCUMENTATION
Each organization should develop a numbering system to
systematically identify and label their SOPs, and the document control should
be described in its Quality Management Plan. Generally, each page of an SOP
should have control documentation notation, similar to that illustrated below. A
short title and identification (ID) number can serve as a reference designation.
The revision number and date are very useful in identifying the SOP in use
when reviewing historical data and is critical when the need for evidentiary
records is involved and when the activity is being reviewed. When the number
of pages is indicated, the user can quickly check if the SOP is complete.
Generally this type of document control notation is located in the upper right-
hand corner of each document page following the title page.
Short Title/ID #
Rev. #:
Date:
Page 1 of

15. CLEANING METHODS INTRODUCTION
Cleaning is one of the major and critical activities in pharmaceutical
operation. It is enough to say that clean environment and clean operations is the
heart of pharmaceutical activities.
The four basic requirements of cGMP are identity, safety, strength and
purity. The concept of purity and safety are directly related to the cleaning
operations.
There are different levels or degrees of cleanliness required in
pharmaceutical operations and naturally the specification of each of the cleaning
will differ substantially.
OBJECTIVES
 The major objective of cleaning methods is to avoid contamination of the
pharmaceutical products or that contamination is reduced to an acceptable level.
 To confirm a reliable cleaning procedure so that the analytical monitoring may be
omitted or reduced to a minimum in the routine phase.

16. OUTLINE OF A CLEANING METHOD
Designing of a cleaning method is an important task. This process of
designing includes
 What is being cleaned? e.g. Equipment, Facilities, Vessels and containers
 What are the contaminants? e g. Micro-organisms, Endotoxins, Dust and fibres
 What is the level of cleanliness expected and what is the acceptance criteria?
 Which cleaning agents to be used and at what concentration?
 Who is going to do the cleaning? Who is going to supervise?
 What record will be maintained?
Once the data related to above points is collected then the required
cleaning method may be adopted.

17. DIFFERENT METHODS OF CLEANING
 Manual cleaning procedures
 Semi-automated cleaning procedures
 Fully automated cleaning procedures
Manual cleaning procedures are operator dependent. It however, does not
mean that they are not effective, if these are carried out by properly trained
operators, they could be superior to automated methods.
But in the semi-automated and automated cleaning procedures, there is
reduced operator involvement. However, this may not always be advantageous as
the operator during manual cleaning can inspect the equipment at every step and
may repeat the step if required.
CLEANING ARRAY
 Equipment disassembly
 Prewash
 Wash
 Initial rinses
 Final rinse
 Reassembly

18. DOCUMENTATION FOR CLEANING
The following aspects to be considered during the documentation of a
cleaning procedure are:-
 Detailed cleaning procedure(s) are to be documented in SOPs.
• When more complex cleaning procedures are required, it is important to
document the critical cleaning steps.
• Other factors such as history of cleaning, residue levels found after
cleaning, and variability of test results may also dictate the amount of
documentation required.
• The cleaning record should be signed by the operator who performed the
cleaning and by the person responsible for Production and should be reviewed
by Quality Assurance.

19. QUALITY CONTROL DOCUMENTATION INTRODUCTION
Good documentation is an essential part of QA/QC system. It defines a
system of information and control, so that misinterpretation or error in oral
communications is minimized.
OBJECTIVES
 To define the specifications of all materials.
 To prevent unambiguous procedures to be followed.
 To allow tracing of the batch history of any product.
TYPES OF QC DOCUMENTS
1. Quality manual
2. Specifications and testing procedures
 For starting and packaging materials
 For intermediate and bulk products
 For finished products
 For containers and closures
3. SOP‟s and records

20. 1. Quality Manual
A quality manual is a documented quality system procedure intended for the
overall planning and administration of activities which impacts quality within an
organization. A quality manual should cover all the applicable elements of the
quality system standards required for an organization.
Purpose of quality manual
 Communicating the organization quality policy, procedures and requirements
 Describing and implementing effective quality system
 Providing the documented bases for auditing the quality system
Quality policy - It is a statement made by the head of the organization on behalf
of the organization, stating the organizations views and concern about quality.

21. 2. Specifications and Testing Procedures
Specification - A document describing in detail the requirements with which the
product obtained during manufacture have to conform.
 Each specification should be approved and maintained by the quality control
unit
 Periodic revisions of the specifications may be necessary to comply with new
editions of the national pharmacopoeia or other official pharma compendia
• Testing procedures described in documents should be validated in context of
available facilities and equipment before they are adopted for routine testing
 For starting and packaging materials
 The designated name and internal code reference;
 The reference, if any, to a pharmacopoeial monograph; and
 Qualitative and quantitative requirements with acceptance limits
 For intermediate and bulk products
Specifications for intermediate and bulk products should be
available if these are purchased or dispatched, or if data obtained from
intermediate products are used in the evaluation of the finished product.

22.  For finished products
- The designated name of the product and the code reference where
applicable;
- The designated name(s) of the active ingredient(s)
- A description of the dosage form and package details;
- The qualitative and quantitative requirements, with acceptance limits;
- The storage conditions and precautions, where applicable; and
- The shelf-life.
 For containers and closures
All containers and closures intended for use shall comply with the
pharmacopeial requirements. Suitable validated test methods, sample
sizes, specifications, cleaning procedure and sterilization procedure, where
ever indicated, should be followed strictly to ensure that these are not
reactive, additive, and adsorptive or leach and neither effects the quality or
purity of the drugs.

23. 3. Standard Operating Procedures (SOPs) and Records
There should be standard operating procedures for the following:
IPQC during packaging
Change control system
Complaint handling and Product recall
Product recall
Stability testing

24. REFERENCES
1. DOCUMENTATION RELATING TO PRODUCT DEVELOPMENT
 Pg: 166 & 247 of Q.A Manual by D.H Shah
 Pg: 206; 363 & 388 of How to practice GMP‟s by P.P Sharma
 Pg: 339 of cGMP for Pharmaceuticals by Manohar A. Potdar
 www.robelle.com/library/papers/step/process.doc
2. STANDARD OPERATING PROCEDURES
 Pg: 255-259 of How to practice GMP‟s by P.P Sharma
 SOP Guidelines by D.H Shah
 Pg: 377 of cGMP for Pharmaceuticals by Manohar A. Potdar
 http://www.epa.gov/QUALITY/qs-docs/g6-final.pdf
 http://www.mtnstopshiv.org/sites/default/files/attachments/SourceDocSOPv2.
pdf
3. CLEANING METHODS
 Pg: 453 of cGMP for Pharmaceuticals by Manohar A. Potdar
 Pg: 79 of How to practice GMP‟s by P.P Sharma
 SOP Guidelines by D.H Shah
 Pg: 70 of Q.A Manual by D.H Shah
 http://www.irjponline.com/admin/php/uploads/1205_pdf.pdf

25. 4. QUALITY CONTROL DOCUMENTATION
 Pg: 230 of cGMP for Pharmaceuticals by Manohar A. Potdar
 Pg: 286 of How to practice GMP‟s by P.P Sharma
 http://www.alspi.com/quality.pdf
 http://microcontacts.com/pdf/quality_manual.pdf
 http://www.optekinc.com/pdf/QualityManual.pdf