1. GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICALSBy
Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
Department of Pharmaceutics
Omar Al-Mukthar University
Al-Bayda, Libya.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

2. CONTENTS Current GMP in manufacturing processes
Packaging and holding of drugs
Finished pharmaceuticals
General provisions
Organization and personnel
Building and facilities
Equipment
Control of components
Containers and closures
Production and process control
Packaging and labeling control
Holding and distribution
Records and reports
Returned savaged drug products
The inspection for compliance with GMP regulations
Controlled substances safeguards
References
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

3. Introduction
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

4. What is GMP ?
GMP is that part of Quality assurance which ensures that the products are consistently manufactured and controlled to the Quality standards appropriate to their intended use
A set of principles and procedures which, when followed by manufacturers for therapeutic goods, helps ensure that the products manufacture will have the required quality.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

5. Good Manufacturing Practices
A basic tenet of GMP is that quality cannot be tested into a batch of product but must be built into each batch of product during all stages of the manufacturing process.
It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

6. Some of the main risks are
unexpected contamination of products, causing damage to health or even death.
incorrect labels on containers, which could mean that patients receive the wrong medicine.
insufficient or too much active ingredient, resulting in ineffective treatment or adverse effects.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

7. Why GMP is important
A poor quality medicine may contain toxic substances that have been unintentionally added.
A medicine that contains little or none of the claimed ingredient will not have the intended therapeutic effect.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

8. GMP QA
GMP QC
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

9. QA, GMP & QC inter-relationship
It is the sum total of the organized arrangements with the objective of ensuring that products will be of the quality required for their intended use QA
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

10. GMP
GMP
Is that part of Quality Assurance aimed at ensuring that products are consistently manufactured to a quality appropriate to their intended use
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

11. QA, GMP & QC inter-relationship
Is that part of GMP concerned with sampling, specification & testing, documentation & release procedures which ensure that the necessary & relevant tests are performed & the product is released for use only after ascertaining it’s quality QC
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

12. QC and QA
QC is that part of GMP which is concerned with sampling,
specifications, testing and with in the organization, documentation,and release procedures which ensure that the necessary and relevant tests are carried out
QA is the sum total of organized arrangements made with the object of ensuring that product will be of the Quality required by their intended use.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

13. QC and QA
Operational laboratory techniques and activities used to fulfill the requirement of Quality
All those planned or systematic actions necessary to provide adequate confidence that a product will satisfy the requirements for quality
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

14. QC and QA QC is lab based QA is company based
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

15. GMP
The Quality of a formulation or a bulk drug depends on the Quality of those producing it
GMP is the magic key that opens the door of the Quality
In matter of GMP, swim with the current and
in matter of Quality stand like a rock!
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

16. GMP helps boost pharmaceutical export opportunities
Most countries will only accept import and sale of medicines that have been manufactured to internationally recognized GMP.
Governments seeking to promote their countries export of pharmaceuticals can do so by making GMP mandatory for all pharmaceutical production and by training their inspectors in GMP requirements.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

17. GMP Covers…
ALL aspects of production; from the starting materials, premises and equipment to the training and personal hygiene of staff.
Detailed, written procedures are essential for each process that could affect the quality of the finished product.
There must be systems to provide documented proof that correct procedures are consistently followed at each step in the manufacturing process - every time a product is made.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

18. GMP guidelines GMP as per Schedule “M” GMP as per WHO
GMP as per MCA now known as MHRA
GMP as per TGA
GMP as per US FDA
GMP as per ICH guidelines
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

19. GMP guidelines GMP as per Schedule “M” www.cdsco.nic.in GMP as per WHO
GMP as per MCA now known as MHRA
GMP as per TGA
GMP as per US FDA
GMP as per ICH guidelines
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

20. GMP guidance documents
EU Good Manufacturing Practice (GMP) Guidelines, Volume 4 of “The rules governing medicinal products in the European Union”
US FDA current Good Manufacturing Practice (cGMP) for finished pharmaceuticals, 21 CFR, 210 and 211
WHO Good Manufacturing Practices for pharmaceutical products, Annex 4 to WHO Technical Report Series, No. 908, 2003
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

21. GMP GMP in solid dosage forms GMP in semisolid dosage forms
GMP in Liquid orals
GMP in Parenterals Production
GMP in Ayurvedic medicines
GMP in Bio technological products
GMP in Nutraceuticals and cosmeceuticals
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

22. Ten Principles of GMP
Design and construct the facilities and equipments properly
Follow written procedures and Instructions
Document work
Validate work
Monitor facilities and equipment
Write step by step operating procedures and work on instructions
Design ,develop and demonstrate job competence
Protect against contamination
Control components and product related processes
Conduct planned and periodic audits
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

23. List of important documents in GMP
Policies
SOP
Specifications
MFR (Master Formula Record)
BMR
Manuals
Master plans/ files
Validation protocols
Forms and Formats
Records
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

24. 10 attributes of a good document
Accurate
Clear
Complete
Consistent
Indelible
Legible
Timely
Direct
Authentic
Authorized
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

25. Beyond GMP Reduce pollution - Zero discharge
Adaptation of environment friendly methods
Consideration for better and healthier life tomorrow
Consideration of ethics in life
One should begin with end in mind otherwise it will be the beginning of the end
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

26. API Manufacturing Process
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

27. Secondary Manufacturing Dosage Forms
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

28. Secondary Manufacturing Process - Tablets
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

29. Secondary Manufacturing Process – Sterile parenteral for injection
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

30. Biotechnology Manufacturing Process
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

31. Current GMP in manufacturing processes (cGMP)
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

32. What are cGMPs?
cGMP refers to the Current Good Manufacturing Practice regulations enforced by the US Food and Drug Administration (FDA).
cGMP provide for systems that assure 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 manufacturers of medications adequately control manufacturing operations
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

33. What are cGMPs?
This includes 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.
This formal system of controls at a pharmaceutical company, if adequately put into practice, helps to prevent instances of contamination, mix-ups, deviations, failures, and errors.
This assures that drug products meet their quality standards.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

34. What are cGMPs?
The cGMP requirements were established to be flexible in order to allow each manufacturer to decide individually how to best implement the necessary controls by using scientifically sound design, processing methods, and testing procedures.
The flexibility in these regulations allows companies to use modern technologies and innovative approaches to achieve higher quality through continual improvement.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

35. What are cGMPs?
Accordingly the “c” in cGMP stands for “current” requiring companies to use technologies and systems that are up-to-date in order to company with the regulations.
Systems and equipment that may have been “top-of-the-line” to prevent contamination, mix-ups, and errors 10 or 20 years ago may be less than adequate by today’s standards.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

36. What are cGMPs?
It is important to note that cGMP are minimum requirements.
Many pharmaceutical manufacturers are already implementing comprehensive, modern quality systems and risk management approaches that exceed these minimum standards.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

37. Why are cGMP so important
A consumer usually cannot detect (through smell, touch, or sight) that a drug product is safe or if it will work.
While cGMPs require testing, testing alone is not adequate to ensure quality.
In most instances testing is done on a small sample of a batch (for example, a drug manufacturer may test 1000 tablets from a batch that contains 2 million tablets), so that most of the batch can be used for patients rather than destroyed by testing.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

38. Why are cGMP so important
Therefore, it is important that drugs are manufactured under conditions and practices required by the cGMP regulations to assure that quality is built into the design and manufacturing process at every step.
Facilities that are in good conditions, equipment that is properly maintained and calibrated, employees who are qualified and fully trained, and processes that are reliable and reproducible, are a few examples of how cGMP requirements help to assure the safety and efficacy of drug products.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

39. Packaging
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

40. Packaging
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

41. Packaging
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

42. Packaging and holding of drugs
Care shall be taken when using automatic tablet and capsule counting, strip and blister packaging equipment to ensure that all ‘rogue’ tablets, capsules or foils from packaging operation are removed before a new packaging operation is commenced.
There shall be an independent recorded check of the equipment before a new batch of tablets or capsules is handled.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

43. Packaging and holding of drugs
Uncoated tablets shall be packed on equipment designed to minimize the risk of cross-contamination. Such packaging shall be carried out in an isolated area when potent tablets or Beta-Iactum containing tablets are being packed.
The strips coming out of the machine shall be inspected for defects such as misprint, cuts on the foil, missing tablets and improper sealing.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

44. Packaging and holding of drugs
Integrity of individual packaging strips and blisters shall be subjected to vacuum test periodically to ensure leak proofness of each pocket strip and blister and records maintained.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

45. Finished pharmaceuticals
Appropriate specifications for finished products shall include: -
The designated name of the product and the code reference.
The formula or a reference to the formula and the pharmacopoeial reference.
Directions for sampling and testing or a reference to procedures.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

46. Finished pharmaceuticals
A description of the dosage form and package details.
The qualitative and quantitative requirements, with the acceptance limits for release.
The storage conditions and precautions, where applicable, and the shelf-life.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

47. General provisions
The processing of dry materials and products creates problems of dust control and cross-contamination. Special attention is therefore, needed in the design, maintenance and use of premises and equipment in order to overcome these problems. Wherever required, enclosed dust control manufacturing systems shall be employed.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

48. General provisions
Suitable environmental conditions for the products handled shall be maintained by installation of air-conditioning wherever necessary. Effective air extraction systems, with discharge points situated to avoid contamination of other products and professes shall be provided. Filters shall be installed to retain dust and protect the factory and local environment
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

49. General provisions
Special care shall be taken to protect against subsequent contamination of the product by particles of metal or wood. The use of metal detector is recommended. Wooden equipment should be avoided. Screens, sieves, punches and dies shall be examined for wear and tear or for breakage before and after each use.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

50. General provisions
All ingredients for a dry product shall be sifted before use unless the quality of the input material can be assured. Such sifting shall normally be carried out at dedicated areas.
Where the facilities are designed to provide special environmental conditions of pressure differentials between rooms, these conditions shall be regularly monitored and any specification results brought to the immediate attention of the Production and quality Assurance Department which shall be immediately attended to.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

51. General provisions
Care shall be taken to guard against any material lodging and remaining undetected in any processing or packaging equipment. Particular care shall be taken to ensure that any vacuum, compressed air or air-extraction nozzles are kept clean and that there is no evidence lubricants leaking into the product from any part of the equipment.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

52. Organization and personnel
Responsibilities of quality control unit.
Personnel qualifications.
Personnel responsibilities.
Consultants.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

53. Organization and personnel
The manufacture shall be conducted under the direct supervision of competent technical staff with prescribed qualifications and practical experience in the relevant dosage and/or active pharmaceutical products.
The head of the Quality Control Laboratory shall be independent of the manufacturing unit. The testing shall be conducted under the direct supervision of competent technical staff who shall be whole time employees of the licensee.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

54. Organization and personnel
Personnel for Quality Assurance and Quality Control operations shall be suitably qualified and experienced.
Written duties of technical and Quality Control personnel shall be laid and following strictly.
Number of personnel employed shall be adequate and in direct proportion to the workload.
The licensee shall ensure in accordance with a written instruction that all personnel in production area or into Quality Control Laboratories shall receive training appropriate to the duties and responsibility assigned to them. They shall be provided with regular in-service training.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

55. Building and facilities
Design and construction features.
Lighting.
Ventilation, air filtration, air heating and cooling.
Plumbing.
Sewage and refuse.
Washing and toilet facilities.
Sanitation.
Maintenance.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

56. Building and facilities
The building(s) used for the factory shall be designed, constructed, adapted and maintained to suit the manufacturing operations so as to permit production of drugs under hygienic conditions. They shall conform to the conditions laid down in the Factories Act.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

57. Building and facilities
The premises used for manufacturing, processing, warehousing, packaging labeling and testing purposes.
Compatible with other drug manufacturing operations that may be carried out in the same or adjacent area / section.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

58. Building and facilities
Adequately provided with working space to allow orderly and logical placement of equipment, materials and movement of personnel so as to:
avoid the risk of mix-up between different categories of drugs or with raw materials, intermediates and in-process material.
avoid the possibilities of contamination and cross- contamination by providing suitable mechanism.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

59. Building and facilities
Designed/constructed/maintained to prevent entry of insects, pests, birds, vermins, and rodents. Interior surface (walls, floors and ceilings) shall be smooth and free from cracks, and permit easy cleaning, painting and disinfection.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

60. Building and facilities
Air-conditioned, where prescribed for the operations and dosage froms under production. The production and dispensing areas shall be well lighted, effectively ventilated, with air control facilities and may have proper Air Handling Units (wherever applicable) to maintain conditions including temperature and, wherever necessary, humidity, as defined for the relevant product. These conditions shall be appropriate to the category of drugs and nature of the operation. These shall also be suitable to the comforts of the personnel working with protective clothing, products handled, operations undertaken within them in relation to the external environment. These areas shall be regularly monitored for compliance with required specifications;
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

61. Building and facilities
Provided with drainage system, as specified for the various categories of products, which shall be of adequate size and so designed as to prevent back flow and/or prevent insects and rodents entering the premises. Open channels shall be avoided in manufacturing areas and, where provided, these shall be shallow to facilitate cleaning and disinfection;
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

62. Building and facilities
The walls and floors of the areas where manufacture of drugs is carried out shall be free from cracks and open joints to avoid accumulation of dust. These shall be smooth, washable, covered and shall permit easy and effective cleaning and dis-infection. The interior surfaces shall not shed particles. A periodical record of cleaning and painting of the premises shall be maintained.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

63. Equipment Equipment design, size, and location.
Equipment construction.
Equipment cleaning and maintenance.
Automatic, mechanical, and electronic equipment.
Filters.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

64. Equipment
Equipment shall be located, designed, constructed, adapted and maintained to suit the operations to be carried out. The layout and design of the equipment shall aim to minimise the risk of errors and permit effective cleaning and maintenance in order to avoid cross-contamination, build-up of dust or dirt and, in general any adverse effect on the quality of products. Each equipment shall be provided with a logbook, wherever necessary.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

65. Equipment
Balances and other measuring equipment of an appropriate range, accuracy and precision shall be available in the raw material stores, production and in process control operations and these shall be calibrated and checked on a scheduled basis in accordance with Standard Operating Procedures and records maintained.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

66. Equipment
The parts of the production equipment that come into contact with the product shall not be reactive, additive or adsorptive to an extent that would affect the quality of the product.
To avoid accidental contamination, wherever possible, non-toxic/edible grade lubricants shall be used and the equipment shall be maintained in a way that lubricants do not contaminate the products being produced.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

67. Equipment
Defective equipment shall be removed from production and Quality Control areas or appropriately labeled.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

68. Control of components General requirements.
Receipt & storage of untested components, drug product containers, and closures.
Testing and approval or rejection of components, drug product containers, and closures.
Use of approved components, drug product containers, and closures.
Retesting of approved components, drug product containers, and closures.
Rejected components, drug product containers, and closures.
Drug product containers and closures.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

69. Control of components
Each tablets compressing machine shall be provided with effective dust control facilities to avoid cross-contamination. Unless the same product is being made on each machine, or unless the compression machine itself provides its own enclosed air controlled environment, the machine shall be installed in separate cubicles.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

70. Control of components
Suitable physical procedural and labeling arrangements shall be made to prevent mix up of materials, granules and tables on compression machinery.
Accurate and calibrated weighting equipment shall be readily available and used for in-process monitoring of tablet weight variation. Procedures used shall be capable of detecting out-of-limits tablets.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

71. Control of components
At the commencement of each compression run and in case of multiple compression points in a compression machine, sufficient individual tablets shall be examined at fixed intervals to ensure that a tablet from each compression station or from each compression point has been inspected for suitable pharmacopoeial parameters like ‘appearance’, ‘weight variation’, ‘disintegration’, ‘hardness’, ‘friability’ and ‘thickness’. The results shall be recorded as part of the batch documentation.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

72. Control of components
Tablets shall be de-dusted, preferably by automatic device and shall be monitored for the presence of foreign materials besides any other defects.
Tablets shall be collected into clean, labeled containers.
Rejected or discarded tablets shall be isolated in identified containers and their quality recorded in the Batch Manufacturing Record.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

73. Control of components
In-process control shall be employed to ensure that the products remain within specification. During compression, samples of tablets shall be taken at regular intervals of not greater than 30 minutes to ensure that they are being produced in compliance with specified in-process specification. The tablets shall also be periodically checked for additional parameters such as ‘appearance’, ‘weight variation’, ‘disintegration’, ‘hardness’, ‘friability’ and ‘thickness’ and contamination by lubricating oil.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

74. Containers and closures
All containers and closures intended for use shall comply with the pharmacopoeial requirements. Suitable validated test methods, sample sizes, specifications, cleaning procedure and sterilization procedure, wherever indicated, shall be strictly followed to ensure that these are not reactive, additive, absorptive, or leach to an extent that significantly affects the quality or purity of the drug. No second hand or used containers and closures shall be used.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

75. Containers and closures
Whenever bottles are being used, the written schedule of cleaning shall be laid down and followed. Where bottles are not dried after washing, they should be rinsed with de-ionised water or distilled water, as the case may be.
For in-process and bulk products. - Specifications for in-process material, intermediate and bulk products shall be available. The specifications should be authenticated.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

76. Containers and closures
All containers and closures intended for use shall comply with the pharmacopoeial and other specified requirements. Suitable samples sizes, specifications, test methods, cleaning procedures and sterilization procedures, shall be used to assure that containers, closures and other component parts of drug packages are suitable and are not reactive, additive, adsorptive or leachable or presents the risk of toxicity to an extent that significantly affects the quality or purity of the drug. No second hand or used containers and closures shall be used.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

77. Containers and closures
Plastic granules shall also comply with the pharmacopoeial requirements including physio-chemical and biological tests.
All containers and closures shall be rinsed prior to sterilization with Water for Injection according to written procedure.
The design of closures, containers and stoppers shall be such as to make cleaning, easy and also to make airtight seal when fitted to the bottles.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

78. Containers and closures
It shall be ensured that containers and closures chosen for a particular product are such that when coming into contact they are not absorbed into the product and they do not affect the product adversely. The closures and stoppers should be of such quality substances as not to affect the quality of the product and avoid the risk of toxicity.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

79. Containers and closures
Whenever glass bottles are used, the written schedule of cleaning shall be laid down and followed. Where bottles are not dried after washing, these shall be finally rinsed with distilled water or pyrogen free water, as the case may be, according to written procedure.
Individual containers of parenteral preparations, ophthalmic preparations shall be examined against black/white background fitted with diffused light after filling so as to ensure freedom from foreign matters.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

80. Containers and closures
Glass Bottles:-
Shape and design of the glass bottle shall be rational and standardized. Glass bottles made of USP Type-I and USP Type-II glass shall only be used. Glass bottles shall not be reused. Before use, USP Type-II bottles shall be validated for the absence of particulate matter generated over a period of the shelf life of the product and shall be regularly monitored after the production, following statistical sampling methods. USP Type-III glass containers may be used for non-parenteral sterile products such as Otic Solutions.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

81. Containers and closures
Plastic Containers.-
Pre-formed plastic containers intended to be used for packing of Large Volume Parenteral shall be moulded in-house by one-continuous operation through an automatic machine.
Blowing, filling and sealing (plugging) operation shall be conducted in room(s) conforming to requirements as mentioned in Table III of Item Entry to the area where such operations are undertaken, shall be through a series of airlocks. Blowers shall have an air supply which is filtered through 0.22µ filters. Removal of runners and plugging operations shall be conducted under a laminar airflow workstation.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

82. Containers and closures
Rubber Stoppers:-
The tuber stoppers used for Large Volume Parenterals shall comply with specifications prescribed in the current edition of the Indian Pharmacopoeia.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

83. Production and process control
Written procedures; deviations.
Charge-in of components.
Calculation of yield.
Equipment identification.
Sampling and testing of in-process materials and drug products.
Time limitations on production.
Control of microbiological contamination.
Reprocessing.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

84. Production and process control
Production control is a process of making sure that production is constantly maintained to produce the products of given specifications.
Control process have several aspects, such as raw materials, tools, in-process materials and finished products.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

85. Production and process control
Production control process can be made effective by:
Setting standards
Measuring the job performing
Getting feedback of results
Taking corrective action
Production controls are to ensure that orders are not misunderstood, standards are not violated and objectives are not shifted unknowing. It is a means of building quality.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

86. Packaging and labeling control
Materials examination and usage criteria.
Labeling issuance.
Packaging and labeling operations.
Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.
Drug product inspection.
Expiration dating.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

87. Packaging and labeling control
Care shall be taken when using automatic tablet and capsule counting, strip and blister packaging equipment to ensure that all ‘rogue’ tablets, capsules or foils from packaging operation are removed before a new packaging operation is commenced. There shall be an independent recorded check of the equipment before a new batch of tablets or capsules is handled.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

88. Packaging and labeling control
Uncoated tablets shall be packed on equipment designed to minimize the risk of cross-contamination. Such packaging shall be carried out in an isolated area when potent tablets or Beta-Iactum containing tablets are being packed.
The strips coming out of the machine shall be inspected for defects such as misprint, cuts on the foil, missing tablets and improper sealing.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

89. Packaging and labeling control
Integrity of individual packaging strips and blisters shall be subjected to vacuum test periodically to ensure leak proofness of each pocket strip and blister and records maintained.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

90. Packaging and labeling control
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

91. Holding and distribution
Warehousing procedures.
Distribution procedures.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

92. Holding and distribution
Prior to distribution or dispatch of given batch of a drug, it shall be ensure that the batch has been duly tested, approved and released by the quality control personnel. Pre-dispatch inspection shall be performed on each consignment on a random basis to ensure that only the correct goods are dispatched. Detailed instructions for warehousing and stocking of Large Volume Parenterals, if stocked, shall be in existence and shall be complied with after the batch is released for distribution. Periodic audits of warehousing practices followed at distribution centers shall be carried out and records thereof shall be maintained. Standard Operating Procedures shall be developed for warehousing of products.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

93. Holding and distribution
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

94. Records and reports General requirements.
Equipment cleaning and use log.
Component, drug product container, closure, and labeling records.
Master production and control records.
Batch production and control records.
Production record review.
Laboratory records.
Distribution records.
Complaint files.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

95. Records and reports
The licensee shall maintain records of different manufacturing activities with regard to each stage of manufacture in-process control, assembling, packing, batch records for the quantity of devices manufactured from each lot of blended granules, duration of work, hourly quantum of production in respect of each item as well as record of each sterilizing cycle of the gaseous method employed.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

96. Records and reports
Records shall be maintained for all disposal of waste.
The records shall be made or completed at the time of each operation in such a way that all significant activities concerning the manufacture of pharmaceutical products are traceable.
Records and associated Standard Operating Procedures (SOP) shall be retained for at least one year after the expiry date of the finished product.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

97. Records and reports
Records of receipt of all labeling and packaging materials shall be maintained for each shipment received indicating receipt, control reference numbers and whether accepted or rejected.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

98. Records and reports
The records of the receipts shall include; a. The name of the material on the delivery note and the number of containers; b. The date of receipt; c. The manufacturer’s and/ or supplier’s name; d. The manufacturer’s batch or reference number; e. The total quantity, and number of containers, quantity in each container received; f. The control reference number assigned after receipt; g. Any other relevant comment or information.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

99. Records and reports The manufacturing records
Serial number of the Batch Manufacturing Record.
Reference to Master Formula Record.
Filter integrity testing records
Leak test records.
Inspection records.
Container washing records.
Environmental monitoring records.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

100. Records and reports
Reports of serious adverse drug reactions resulting from the use of a drug along with comments and documents shall be forthwith reported to the concerned licensing authority.
Reference numbers of relevant analytical reports.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

101. Returned savaged drug products
Returned drug products.
Drug product salvaging.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

102. Returned savaged drug products
Adequate areas shall be designed to allow sufficient and orderly warehousing of returned or recalled products.
Segregation shall be provided for the storage of rejected, recalled or returned materials or products.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

103. The inspection for compliance with GMP regulations
Short description of the self inspection system indicating whether an outside, independent and experienced external export was involved in evaluating the manufacturer’s compliance with Good manufacturing Practices in all aspects of production.
Periodic inspection of the garments shall be done by responsible staff.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

104. The inspection for compliance with GMP regulations
When inspection is done visually, it shall be done under suitably controlled conditions of illumination and background.
Operators doing the inspection shall pass regular eye-sight checks with spectacles, if worn, and be allowed frequent rest from inspection.
Where other methods of inspection are used, the process shall be validated and the performance of the equipment checked at suitable intervals. Results shall be recorded.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

105. The inspection for compliance with GMP regulations
Inspection of equipment for cleanliness immediately before use;
Clarity testing inspection units.
Tablet Inspection unit/belt.
Visual inspection area
Medical inspection of workers at the time of employment and periodically check-up thereafter at least once a year.
Needle Inspection Unit.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

106. Controlled substances safeguards
Hazardous, toxic substances and flammable materials shall be stored in suitably designed and segregated, enclosed areas in conformity with Central and State Legislations.
Highly hazardous, poisonous and explosive materials such as narcotics, psychotropic drugs and substances presenting potential risks of abuse, fire or explosion shall be stored in safe and secure areas. Adequate fire protection measures shall be provided in conformity with the rules of the concerned civic authority.
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

107. References
EU Good Manufacturing Practice (GMP) Guidelines, Volume 4 of “The rules governing medicinal products in the European Union”
US FDA current Good Manufacturing Practice (cGMP) for finished pharmaceuticals, 21 CFR, 210 and 211
WHO Good Manufacturing Practices for pharmaceutical products, Annex 4 to WHO Technical Report Series, No. 908, 2003
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.

108. E-mail: nanjwadebk@gmail.com
2014/01/12
Department of Pharmaceutics, Omar Al-Mukthar University, Al-Bayda, Libya.