Definition- A piece of written, printed or electronic matter that provides information or evidence that severs as an official record.
Revise schedule M has the following elements which are related to documentation
- Documentation and records
- Master formula record
- Packaging records
- Batch packaging records
- Batch processing records
- Standard operating procedures
All these records are included in the WHO GMP text under the element documentation.
A
good documentation is an essential part of the quality assurance system. There
for every manufacture of the drugs should have good documentation.
Aim of the documentation are-
1. To define specification for all materials
2. To define methods of manufacture and control
3. To ensure that all personnel connected with manufacture and quality control know what to do and when to do.
4. To ensure that personnel authorized to release the batch sale or reject it have all information that is necessary to take the decision.
5. To provide information during investigation, if a batch is suspected to have defect.
6. To make available data needed for validation, review and statistical analysis.
Following points should be consider while designing the documents
1. Document can be batch related or general. Content of the document should include title, nature and purpose. Below mentioned questions must be answered by process records
-
What to do?
-
Where to do?
-
When to do?
-
How to do?
-
Who will do it?
- Why to do?
2. While designing and preparing records, national legislation regulating manufacture of drugs should be taken into consideration. In India Schedule U and Schedule M to the drug and cosmetics rules may be referred.
3. Documents should be laid down in an orderly fashion so that these can be checked easily.
4. Reproduced records should be legible and clear. The reproduction process should not allow any error when working documents are reproduced from master document.
5. Documents should be prepared by the person intimately connected with the work or expert of the field and should be regularly reviewed and kept up to date.
6. No document should be changed without authorization from appropriate authority.
7. When a document is revised it should be ensured that suspended version is not circulated.
8. Where entries are made in the document, these should be clear, legible and indelible. If an error is made while making entries or error is detected later on, it should be corrected in such a manner that original entry is not lost and the correct is made close to it and initiated.
9. Now a days data may be recorded by electronic data processing system. If such a system is used, only authorized persons should be allowed to enter or modify data in computer. Access to such data should be restricted by passwords or other suitable methods.
10. WHO GMP guidelines recommend that records should be retained for at least one year after expiry date of finished product.
Master Formula
Record (MFR)
The Indian and WHO GMP require a manufacturer of the
drugs to maintain Master Formula Records for each product. These records should
be prepared by competent technical staff and should be reviewed by the head of
the production and quality control departments. Units which have research and
development department should associate this department also and Master Formula
Record should be reviewed by the heads of these departments.
MFR for each drug product shall describe all aspects of its manufacture, packaging and control. To assure uniformity from batch to batch, MFR shall be prepared for each batch size separately and should be dated and signed by one person and independently checked, dated and signed by at least second person.
“Master Formula Record is a product specific document
compiled, checked, authorized and approved by competent technical personnel
from product development, production, packaging and quality control
department.”
MFR should include-
1. Name and strength of the product along with dosage form (trade name) and batch size.
2. The name and weight/measure of active ingredients per dosage unit or per unit weight/measure of the product and total weight / measure of any dosage unit.
3. A complete list of all the ingredients to be used in the manufacture of the product indicating any special characteristics.
4. An accurate statement of weight/measure of each ingredient (same weight system should be used) required as per formula of dosage form and the weight/measure actually to be used (e.g. overages to compensate losses during storage).
5. A statement of theoretical yield including permissible limits beyond which investigation is required including final yield with acceptable limits.
6. A description of containers, closures and packaging materials to be used.
7. A description of all vessels, equipment to be used in their preparation and methods or reference to the methods to be used for preparing and operating critical equipment .
8. Stepwise processing and packaging instructions.
9. In process quality control to exercised during processing and packaging with their limits.
10. Precautions to be taken during manufacture and storage of semi-finished product including any special storage conditions
11. Requirements for storage of the products including the container, the labeling and any special storage conditions.
Batch Formula
Record (BFR)
Batch Formula Records are required to be maintained
for each batch of the product manufactured. These should be based on MFR. Method
of preparation of Batch Formula Record should be such that transcription errors
do not occur.
Before ant process begins, a check should be made to
ensure that all work stations are clear of previous products, materials and
documents. This check should be recorded.
During the processing, information listed below should
be recorded, signed and dated by the person responsible for processing
operations:
1. Name
of the product
2. Batch
number
3. Date
of commencement and completion of significant intermediate stage
4. Name
of the person responsible for each stage of production
5. Initial
of operator who carried out significant processes and initials of person who
checked, wherever applicable
6. Quantity,
batch number, quality control report number of each ingredients actually
weighed and amount of any recovered material added
7. In
process controls carried out their results and signature of person who
performed it
8. Theoretical
yield and actual yield at appropriate stage of production together with
explanation, if variation beyond expectation observed.
9. Authorization
if any deviation made. Usually flow sheets are prepared by the pharmaceutical
industry for different pharmaceutical dosage form.
10. Complete
labeling control records, including specimen or copies of all labeling used.
11. Description
of drug product containers and closures; this should incude primary, secondary
and pointed packaging materials.
12. Any
sampling performed, during the production and/ packaging activity.
13. Results
of examination made.
Standard Operating
Procedures (SOPs)
One
of the important activities is the implementation GMPs is preparation of SOPs. One
of the objectives of GMP is consistency in quality. Consistency in quality can
be achieved by minimizing sources of quality variation.
|
Sources of variation |
Sources of quality
variation |
|
Materials |
-Variation between
suppliers of the same substance - variation between
batches from the same suppliers - Variation within
batch |
|
Machines |
-Variation of Equipment
for the same process -Difference in
adjustment for same process -Aging and improper
care |
|
Methods |
-inexact procedure -inadequate procedure -Negligence by chance |
|
Men |
-improper working
condition - inadequate training
and understanding - lack of interest and
emotional upheavals - dishonesty, fatigue
and carelessness |
These
sources of quality variations are required to be controlled. Preparation of
SOPs is a step in this direction.
“SOPs can be defined as
written documents specifying the procedures that must be followed to carry out
operations.” The basic purpose of SOP is to
reduce the introduction of errors and variation in the operation. Other purpose
of SOPs is of historical perspective i.e. how to carry out operation.
Benefits of SOPs
preparation-
1. Since
SOPs outlined the critical aspects of procedure, they help to assure that these
aspects are appropriately emphasized while carrying out the procedure.
2. Individual
need not rely on memory or word of mouth communication procedure. This helps to
prevent introduction of errors and variations.
3. SOPs
can be used to train personnel. Personnel under training can clarify the
aspects which have not been clearly understood by them. This helps to prevent
misunderstanding.
4. Preparing
SOPs will require an individual to think the whole operation and the procedure
to be described. In doing this he can identify the potential problems and their
solutions. Thus SOPs improves planning and organization.
5. SOPs
eliminate need to redevelop the procedure every time an operation is performed.
Following are the
guidelines to prepare SOPs-
1. Give
clear and descriptive title to each SOPs
2. Provide
sufficient details. The SOP should meet the need of individual; all the same,
it should be general enough for more than one user.
3. 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.
4. Organize
SOPs according to order of sequence of events involved in performing the
operation. Write the text in a straight forward and easy to follow manner.
5. After
drafting SOP, use it in performing the operation to ensure that it has
sufficient details to perform the operation in intended manner.
6. Take
into account the instructions from the manufacturer of the equipment which is
employed in performing the operation while drafting SOP.
7. Indicate
total no of pages so that user is certain that he is performing the complete
operation.
8. Indicate
the effective date of SOP.
The best way to prepare SOPs is to involve at least
one person from each work area. The person selected should be asked to write
down the procedure of the operation with details and the precautions to be
taken. The written procedure should be discussed in the group of person
intimately connected with the operation. Modification, if any, should be made.
It will be advised to first prepare SOP for SOP, to reduce variation from
SOP to SOP. The following points should be considered while preparing SOP on
SOP-
1. Design
a format for SOP. This will maintain uniformity in writing SOPs.
2. Device
a system of assigning number to SOP. This may include a code for department,
activity to which it is related and version. For example, SOP for equipment
cleaning in production department may be numbered as PR/EC/01/V1 or PR.EC.01.V1.
3. Device
a date format. Date format could be DD/MM/YYYY or DD/MM/YY.
4. Define
elements of SOP, usually the following elements are included in a SOP:
-
SOP no
-
Title of SOP
-
Department
-
Prepared by, approved by,
authorized by or issued by
-
Purpose/ object
-
Scope
-
Responsibility
-
Procedure
-
References
-
Distribution
SOPs
may require revision in event of availability of better technology, improvement
in efficiency of method etc. SOPs may revised when it become necessary. The changes
made in the SOP should be authorized by the management. Date of revision of SOP
and date of its effectiveness should appear in the SOP. It should be ensured
that user uses the revised SOP after the date of effectiveness. All old SOPs
should be withdrawn. A copy of old SOP may be retained for records.
SOPs
pertinent to the work in an area must be immediately available in that area and
should be accessible to the user. If it is not available readily, the user is
not likely to retrieve them for reasons like time pressure or incontinence.
They may carry out the operation without consulting SOP and may not carry out
the operation in intended manner.
WHO
guidelines require that at least, the following SOPs should be available
1. Receipt,
handling and internal labeling of starting materials, primary packaging
materials and printed materials
2. Major
equipment and instrument calibration and validation
3. Sampling
4. Batch
numbering system
5. Testing
of material at different stages of manufacture, describing method and equipment
to be used
6. Release
and rejection of the materials and finished products
7. Handling
of Analytical instruments and calibration
8. Facilities
and equipment maintenance, cleaning and sanitization
9. Personnel
(training, clothing, hygiene)
10. Environmental
monitoring
11. Pest
control
12. Complaints
13. Recall
14. Returns
Records
WHO
guidelines require records to be maintained. The main records to be maintained
include
1. Receipt
and issue record of starting materials , primary packaging material and printed
material
2. Written
release and rejection procedures for material including release of finished
products
3. Log
book for assigning batch number
4. Equipment
cleaning and use log
5. Component,
drug product container, closure and labeling records
6. Master
production and control records
7. Batch
production and control records
8. Laboratory
records
9. Analysis
records
10. Finished
product distribution record
11. Analytical
instruments and calibration record
12. Complaint
files,
13. Recalls
14. Returns
15. Housekeeping,
maintenance, cleaning and sanitization records
16. Personnel
matters including qualification, training, etc
17. Environmental
monitoring
Distribution Records
“Distribution
records are written data related to distribution of drug products from the
manufacturer to the distributors.” These records are maintained in such a way
that batches of drug products is easily available. It is important that
information should be easily available so that the product recall is efficient
in case there is complaint or adverse reaction due to use of the drug product.
Every distributor is also obliged to maintain a complete and accurate record of
further distribution.
An
inventory card may be maintained to find out stock position quickly. A
distribution register may be maintained for detailed information about
distribution of each batch of drug product.
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