Good Manufacturing Practices Flashcards
Ensuring quality offers….?
- Offers the assurance that a healthcare professional prescribing or administering the drug is confident of each unit’s efficacy
- Protects the public against potential hazards caused by accidental manufacturing and design defects, or instructions for product usage/storage
Quality determined by?
- Identity: Active ingredient
- Purity: Not contaminated with potentially harmful substances
- Potency: Usually 90–110% of the labeled amount
- Uniformity: Consistency of color, shape, size
- Bioavailability
- Stability: Ensuring medicine activity for stated period
Importance of cGMP?
• Assures proper design, monitoring, and control of manufacturing processes and facilities
• Adherence to the cGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that drug manufacturers adequately control manufacturing operations
• Establishing strong quality management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories
• Helps to prevent instances of contamination, mix-ups, deviations, failures, and errors
• Assures that drug products meet their quality standards
Impacts of poor-quality meds
• Poor efficacy which may result in prolonged illnesses and/or death
• High Health Bills
• Toxicity, severe adverse effects
• Loss of credibility
• Wastage of materials
• Wastage of finances
Good Manufacturing Practice
- Set of regulations, codes, and guidelines for the manufacture of drug substances and drug products, medical devices, in vivo and in vitro diagnostic products, and foods
• Part of quality assurance ensuring that products are:
- consistently produced
- controlled to the quality standards appropriate to their intended use and as required by the marketing authorization
Objectives of cGMP
• Guarantee high quality products
• Products safe and free of contamination
• Efficient and stable products
Components of GMP
• GMP is a part of Q.A
•GMP’s main function is to produce quality products consistently
• GMP must meet legal requirements of country
• GMP must meet both production and Q.C. related issues
-WHO further comments that the main function of GMP is to avoid mix-ups
Areas covered by cGMP
- General considerations
- Personnel
- Premises
- Equipment
- Sanitation
- SOP’s
- Raw Materials
- Self Inspection And Audit
- Master Formula Records
- Batch Manufacturing Records
- Warehousing Area
- Labels And Other Printed Materials
- QA
warehousing areas
- Should be designed and adapted to ensure good storage conditions
- Should be clean, dry and maintained with acceptable temperature limits
- Should have appropriate house-keeping and rodents, pests and vermin control
- Separate sampling area for active raw material and excipients
- Receiving bay separate from outgoing bay
- Every material stored should be labeled properly
- Fire Prevention
Potential Risks in Manufacturing
- Contamination of products (microbial, particulate or other)
- Incorrect labels on containers
- Insufficient active ingredient
- Excess active ingredient
- Poor quality raw materials
- Poor formulation practices
Calibration
The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (especially weighing), recording, and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard
Design features
- Minimize risks of errors
- Permit effective cleaning
- Permit effective maintenance
- Avoid cross-contamination, build-up of dirt and dust
- Maximum protection against entry of insects, birds and animals
- Separate facilities for other products such as some antibiotics, hormones, cytotoxic substances
- Finishing floors, walls, and Ceilings should be smooth, impervious, hard-wearing, easy to clean
- Specific Areas: Production areas, Quality control areas, Weighing areas, Storage areas, Ancillary areas, Hygiene
Validation
Action of proving (in accordance with principles of GMP) that any procedure, process, equipment, material, activity, or system actually leads to expected results
General considerations
- Compliance with GMP
- Consistent uniform batches
- Location And surroundings
- Water system
- Disposal Of Waste
Design and construction features
- Any building used in the manufacture, processing, packing, or holding of a drug product shall be of suitable size, construction and location to facilitate cleaning, maintenance
- The orderly placement of equipment and materials to prevent mix-ups between different components, drug product containers, closures, labeling, in-process materials, or drug products, and to prevent contamination
- Lighting: Adequate lighting shall be provided in all areas
- Ventilation, air filtration, air heating and cooling
- Equipment for adequate control over air pressure, micro-organisms, dust, humidity
Qualification
Action of proving that any premises, system, and items of equipment work correctly and actually lead to expected results
Plumbing
Potable water shall be supplied under continuous positive pressure in a plumbing system
Air filtration systems
Including prefilters and particulate matter air filters shall be used when appropriate on air supplies to production areas
Lighting
Adequate lighting shall be provided in all areas
Sanitation
Building shall be free of infestation by rodents, birds, insects, and other vermin. Trash and organic waste matter shall be held and disposed of in a timely and sanitary manner. There shall be written procedures for use of suitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents
Sewage and refuse
Sewage, trash, and other refuse in and from the building and immediate premises shall be disposed of in a safe and sanitary manner
Raw materials
- An inventory should be maintained for raw materials to be used at any stage of manufacturing. Records should be maintained as per Schedule U.
- Raw materials should be purchased from approved sources, must be checked by QC department on receipt, and should be labeled
Maintenance
Any building used in the manufacture, processing, packing, or holding of a drug product shall be maintained in a good state of repair
Exhaust systems
must be adequate to control contaminants
Ventilation, air filtration, air heating and cooling
Equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature shall be provided when appropriate for the manufacture, processing, packing, or holding of a drug product
Washing and toilet facilities
Adequate washing facilities shall be provided, including hot and cold water, soap or detergent, air driers or single-service towels, and clean toilet facilities easily accessible to working areas
Drains
Shall be of adequate size and, where connected directly to a sewer, shall be provided with an air break to prevent back siphonage
Self Audit & Inspection
Regular independent inspection is necessary to evaluate the manufacturer’s compliance with GMP in all aspects of manufacturing. Procedures shall be documented: Evaluation, Conclusion, Recommendations for Corrective action
Standard Operating Procedure
There shall be written Standard Operating Procedure for each operation including for equipment, sampling, testing, process, packaging
Equipment
Equipment shall be located, designed, constructed, adapted and maintained to suit the operation to be carried out. Should be made of non-reactive material, such as High grade of steel (316,302). Equipment should be calibrated, checked, labelled, sterilized, and accompanied with SOP
Packaging and Labeling Operations
- Prevention of mix-ups and cross-contamination by physical or spatial separation from operations on other drug products
- Examination of packaging and labeling materials for suitability and correctness before packaging operations, and documentation of such examination in the batch production record
adultered or misbranded
An OTC drug product for retail sale, not packaged in a tamper-resistant package or not properly labeled
Drug product inspection
- Examination of packaged and labeled products during finishing operations to provide assurance that containers and packages have the correct labeling
- Collection of a representative sample of units at the completion of finishing operations for visual examination for correct labeling
- Recording the results of these examinations in the batch production or control records
Required records for Packaging & Labeling Control
- Materials examination and usage criteria
- Receipt, examination or testing, and whether accepted or rejected
- Storage of labels and other labeling materials separately with suitable identification
- Visual inspection for correct labeling
- Labeling issuance
What to do so as to make it evident to consumer that tampering has occurred?
Package the product in a tamper-evident package
Expiration dating
- To assure that a drug product meets applicable standards, it shall bear an expiration date determined by appropriate stability testing
- If the drug product is to be reconstituted at the time of dispensing, its labeling shall bear expiration information for both the reconstituted and un-reconstituted drug products
- Expiration dates shall appear on labeling in accordance with the requirements
Quality Assurance
- The main objective is to ensure the products are of the quality required for their intended use
- Functions include adequate control measures for manufacturing, supply, and the use of correct starting and packing material
- Adequate control on starting material, intermediate, and bulk products
- Process validation in accordance with established procedures
BOMRA Functions include….?
- Licensing and Inspection of Pharmaceutical operations
- Authorisation of imports
- Registration of medicine and related substances
- Post Marketing Surveillance - Pharmacovigilance
- Testing of medicine and related substances
- Clinical Trials Authorisation
Good compounding practice
Premises, Personnel, PPE, Equipment (e.g., mortar and pestle, glassware, measuring cylinders), SOP, Compounding calculations record
Extemporaneous compounding
- Good compounding practices ensure the drug has the identity, strength, and meets the quality and purity characteristics it is represented to possess
- Patients may need drug dosages or strengths not commercially available
- Some patients are allergic to excipients in commercially available products
- Some medications require preparation and dispensing every few days and are not suitable as manufactured products
Prescription Label
- The name and address of the pharmacy
- The serial number of the prescription
- Expiry
- The name of the patient
- Directions for use including any precautions, as indicated on the prescription
- The address of the patient
- Name of the dispensing pharmacist
- Contact details of the pharmacy
- The drug name, strength, and manufacturer’s lot or control number
