Good documentation is a crucial part of Quality assurance. The structure and design of the document rests in the hands of manufacturer
It helps
- In providing procedures and specifications for materials, manufacturing method and control which in turn help the personnel to know what and when to do
- Authorized persons to have the necessary information to take a decision on releasing the batch of drug for sale
- In providing documented evidence and easy traceability during audit that aids in investigation
- Making the data available for statistical analysis, review and validation
General
- Documents should be prepared and designed with care and in compliance with manufacturing and marketing authorizations
- They should be approved with dated signature from responsible person. No changes should be made with approval.
- The content in the documents should be unambiguous with proper title and purpose in clear manner.
- The documents that are reproduced should be legible, clear and should not allow introduction of error through reproduction process
- They should be regularly checked and updated. There should be a proper system to prevent use of superseded version of it.
- Sufficient space should be provided for entry of signature, date and other entries needed.
- Any changes made to the document should be with dated signature. Every alteration made should allow for reading the original information but should not deviate from original content. If needed the reason for alteration should also be recorded.
- Records should be done in a manner to trace all the significant activities in manufacturing of product. They should be kept for a minimum period of one year after the expiry date of finished product.
- Data must be recorded by electronic data processing systems allowing authorized persons to make the changes. Any change should be recorded. The access to system should be restricted by passwords.
- Batch records should be protected by back up transfer on paper printouts or microfilm or magnetic tape. During the period of retention the data should be available.
Requirement of Documents
Different kinds of documents should be maintained throughout the quality assurance process. They include
- Bill of Materials
- Protocols
- Policies
- Batch Record Forms
- Standard Operating Procedures (SOPs)
- Test Methods
- Work Instructions
- Log Sheets
- Checklist
- Training Assessments
- Validation documentation
- Technical transfer reports
- Electronic Quality records
- Labels
Starting and packaging materials
Documents providing specifications for the starting, primary & printed packaging materials and description of materials should be provided in addition to the following:
- Designated name & internal code of reference
- Reference to pharmacopoeial monograph
- Quantitative and qualitative requirements with acceptance limits
The following can be added depending on the company
- Specimen of printed materials
- Storage conditions and precautions
- Supplier and original producer of materials
- Maximum period of storage before reexamination
- Sampling and testing directions
The documents for testing should also include the frequency for re assaying starting materials determined by its stability.
Packaging material should be compatible with drug product and be in accordance with the specifications.
Intermediates and bulk products
Document Specifications for intermediate and bulk products should be provided as for starting materials
Finished products
Document specifications should be given by including the following:
- Name and code reference of the product
- Name of the active ingredients
- Formula or reference to it
- Dosage form description and package details
- Sampling and testing directions or reference to the procedures
- Qualitative, quantitative requirements with acceptable limits
- Shelf life of the product
- Storage conditions and precautions to be taken
Master formula
Document with authorized master formula should be present for each product and batch size that need to be prepared
The document should include the following:
- Product name with code reference
- Description of dosage form with its strength and batch size
- Starting materials with quantity to be used, describing name and reference
- Final and intermediate yields with acceptable limits
- Processing location and equipment used
- Methods used for operating and preparing the equipment in assembling, cleaning, sterilizing, calibration and during other use.
- Step wise processing instructions with mixing time, temperature, pretreatment, materials check and sequence of adding materials
- Storage requirements with labeling
Packaging instructions
Document with packaging instructions for each product, pack size and type should be given. In addition it should include:
- Product name
- Description of dosage form with its strength
- Pack size should be expressed in number, volume or weight of the product in final container
- List of materials with their batch size, quantities, sizes and types and reference code
- Reproduction of the printed material with batch number and expiry date
- Description of packaging operation with subsidiary operation and equipment
- In process control details with sampling procedures and acceptance limits
Batch processing record
For every batch BPR should be maintained with approved specification. They should be designed in a way to reduce or eliminate errors.
Before the processing begins, work station should be cleared of products, materials or documents which are not required for the process. The equipment should be clean and suitable for use; this complete checking process should be documented.
During the processing, the following information should be recorded and at the end it should be approved with a dated signature.
- Product name
- Batch number
- Time and date of commencement with intermediate stages and complete production
- Person in charge of each production
- Initials of the person who operates with appropriate person in charge of every step in production
- Analytical control number or batch number and quantity of starting material
- Major equipment used with relevant processing operation
- In process controls with initial of the person carrying out the operation
- Yield of the product at various stages
- Special problems should be notified with authorized signature and also details should be included on why the deviation has occurred from the master formula
SOPs & Records
Standard operating procedures and records of action taken should be available for the following:
- Equipment validation and assembly
- Calibration and analytical apparatus
- Cleaning, sanitization and maintenance
- Environmental monitoring
- Complaints
- Pest control
- Returns
- Recalls
- Personnel matters including clothing, training, hygiene and qualification
Standard operating procedures and records should be there for receipt of delivery of starting & primary & printed packaging material.
The records maintained for receipts should include the following:
- Delivery note should have name of the material and container
- Code of the material or in house name
- Date of receipt
- Supplier or manufacturer’s name
- Manufacturer’s reference or batch number
- Number and total quantity of the containers received
- Batch number should be assigned after the receipt
- Any comments should be addressed
Each piece of equipment and instrument should have standard operating procedures placed close to them.
Standard operating procedures should be available for internal labelling, storage of starting and materials and quarantine
SOP’s for sampling procedure should be provided which specifies the duties of the person performing sampling
Instructions for the sampling should include the following
- Sampling method and sampling plan
- Equipment used
- Precautions on avoiding contamination of material or degradation of quality
- Quantity of sample
- Type of sample container used
- Precautions on sampling of noxious or sterile material
Standard operating procedure should describe the details of batch numbering system to ensure that product at any stage is identified with a specific batch number
SOPs applied to processing stage and retrospective packaging stage should relate to each other
SOP should ensure that uniform batch number should be used throughout even during reprocessing
Allocation of Batch number should be recorded immediately in a logbook with date, product identity & size of the batch
At different stages of manufacturing written procedures should be provided for describing equipment & method used. Record the test performed.
Analysis records should include:
- Product & material name
- Batch number with manufacturer or supplier name
- References to specifications & procedures
- Testing Date & reference number
- Initials of person who has done testing
- Initials of person who verified calculations and testing with date
- Statement of release & rejection with date and signature should be given prior to release of finished product by authorized person
Uses of critical and major equipment should be recorded in chronological order along with areas where they are processed
Written procedures for cleaning and sanitation should be given with schedules, materials and equipment’s used and methods for cleaning equipment’s.
Testing procedures
- Testing procedures that are described in the documents should be validated in the available circumstances of equipment’s & facilities before applying for routine testing
- Documents should be dated with appropriate authorization including tests on content, identity, quality and purity for the materials.
- Specifications should be given on the water, reagents & solvents used along with appropriate signature and approval.
- These specifications should be maintained in documentation centre, quality control & quality assurance
- Periodical review of specifications should be in accordance with national pharmacopoeia & official compendia
- Reference standards, materials, spectra and pharmacopoeia should be in QC lab.
Labels
Labels given to the products or equipment should be clear, unambiguous and in accordance with the company rule.
The words used should be with colors for clear depiction
Finished products should be identified by labelling in accordance to National Legislation with the following:
- Product name
- List of Active ingredients with quantity of each content with their unit value like in weight/volume/dosage units
- Expiry date should be given in uncoded form
- Storage conditions
- Directions on use, precautions & warnings
- Manufacturers name & address or supplier name & address or person responsible for releasing the product in the market
- Label should also indicate concentration, manufacturing date, expiry date, storage conditions & control number
