1. MATERIALS MANAGEMENT KHADIJAH ADE-ABOLADE MPH. FPCPharm.
Chief Regulatory Officer/Lead Inspector
Drug Evaluation & Research
NAFDAC

2. OBJECTIVES
To discuss the requirements for materials management in pharmaceutical manufacturing
Highlight specific requirements for the different types of materials in pharmaceutical manufacturing
Highlight specific requirements for the different types of materials in pharmaceutical manufacturing

3. OUTLINE Types of pharmaceutical materials
General requirements for materials management
Specific requirements for the different types of materials
Conclusion

4. TYPES OF PHARMACEUTICAL MATERIALS
Starting materials
Packaging materials
Intermediate and bulk products
Finished products
Rejected materials
Recalled products
Returned goods
Reagents and culture media
Reference standards
Waste materials
Miscellaneous materials

5. PERSONNEL
Personnel performing work affecting the material or product quality, including third parties, should have an adequate combination of training, education, and experience to carry out that work.
Personnel dealing with hazardous materials should be given specific training and should be provided with the necessary protective equipment.

6. PERSONNEL
Wear clean protective apparel to protect materials and products from contamination by personnel activities
Personnel dealing with hazardous materials should be given specific training and should be provided with the necessary protective equipment.

7. SOURCING Purchasing Not an administrative activity
Staff responsible for purchasing of materials, have sufficient knowledge of the materials, products and their suppliers
To ensure that the correct materials are supplied, purchase materials direct from the API manufacturer or reputable suppliers

8. SOURCING Supplier Qualification
A system that assures that a supplier’s product is produced under controlled conditions, resulting in consistent quality conformance.
Based on the principle of defect prevention, rather than defect detection and inspection
QC and other relevant departments should evaluate and approve suppliers based on their history, nature of the materials and ability of the suppliers to meet established specifications

9. SOURCING Supplier Qualification
Audit of the supplier’s manufacturing facility, where possible or by proxy.
Confirm the quality systems in place at the supplier end meet GMP
Establish that material quality will meet your quality specifications
Capacity to meet your production needs
Where a material may be supplied from more than one plant of the supplier, each plant must be treated as a separate entity for certification purposes.

10. SOURCING Transportation and Materials in Transit
Pharmaceutical starting materials should be transported in accordance with procedures such that:
The identity of the product is not lost.
The product does not contaminate and is not contaminated by other products.
Adequate precautions are taken against spillage, breakage, misappropriation and theft.
Appropriate environmental & storage conditions are maintained.

11. SOURCING Transportation and Materials in Transit
Transportation of materials containing hazardous substances in safe, suitably designed, secured containers and vehicles.
Immediate cleaning of spillages according to written procedures to prevent possible contamination, cross-contamination and hazards.
Damage to containers and any other event or problem that occurs during transit must be recorded and reported

12. RECEIPT Receiving and dispatch bays
Materials and products should be protected from weather during loading and offloading.
An area to clean incoming materials and containers should be provided.
The SOP for receiving materials is an important SOP.
Ensure that the correct materials are received from the correct supplier in the correct quantity and other relative quality parameters

13. RECEIPT Consignment Checks
Each consignment of materials should be accompanied by the manufacturer’s COA of the batch and the MSDS of the material
Note that the supplier’s COA may be accepted provided the FPP manufacturer has established the reliability of the supplier’s analysis through appropriate periodic validation of the supplier’s results and on-site audits of supplier’s facilities.
The COA must be original or authenticity should be assured

14. RECEIPT Consignment Checks
Inspection for possible contamination, tampering and damage, and any suspect containers or, if necessary, the entire delivery should be quarantined for further investigation.

15. RECEIPT Consignment Checks
Cleaning of all containers before taking into the premises, proper labelling with relevant information (e.g. status, name of the material, reference code etc.).
Where additional labels are attached to the containers, the original information should not be lost e.g. expiry dates

16. STORAGE
Materials should be handled and stored in a manner as to prevent degradation, contamination and cross-contamination
Appropriate temperature and relative humidity conditions within defined limits provided, controlled, monitored and recorded
Materials should be stored on pallets or racks to facilitate cleaning, inspections, and pest trap placement.
Orderly manner using proper materials management principles and stock rotation (FEFO)

17. STORAGE ON THE LABEL MEANS “Do not store over 30 °C” from+2°Cto+30°C
“Do not store below 8 °C”
from+8°Cto+25°C
“Protect from moisture”
no more than 60% relative humidity in normal storage conditions; to be provided to the patient in a moisture-resistant container.
“Protect from light”
to be provided to the patient in a light-resistant container.

18. STORAGE
Integrated pest management and control programs which should typically involve a combination of both chemical and non-chemical prevention and control techniques.
Rodents can usually be controlled by the placement of baitless traps; the use of poison bait is not acceptable in a pharmaceutical establishment.
Insects are frequently eliminated by the use of electric exterminators, whereas birds may be trapped

19. STORAGE
Storage Areas
Sufficient capacity to allow the orderly storage of the various categories of materials
Designed to ensure good storage conditions, they should be clean and dry and maintained within acceptable temperature limits
Required special storage conditions should be provided, checked, monitored and recorded
Adequate ventilation, air filtration, air heating and cooling, exhaust system shall be provided within the storage areas

20. STORAGE
Storage Areas
Any system replacing physical quarantine should provide equivalent security
Physical or other equivalent validated (e.g. electronic) segregation should be provided for the storage of rejected, expired, recalled or returned materials or products
Rejected materials and products should be identified and controlled under a quarantine system designed to prevent their use until a final decision is taken on their fate.

21. STORAGE
Storage Areas
Highly active and radioactive materials, narcotics and other hazardous, sensitive and/or dangerous materials and pharmaceutical products, as well as substances presenting special risks of abuse, fire or explosion, (e.g. combustible liquids and solids and pressurized gases) should be stored in a dedicated area that is subject to appropriate additional safety and security measures.

22. QUALITY CONTROL Sampling
There should be a separate sampling area for starting materials in a controlled environment
Sampling facilities should be designed to:
Prevent contamination of the opened container and the materials;
Prevent cross-contamination by other materials, products and the environment and;
Protect the sampler and the material during the sampling procedure.

23. QUALITY CONTROL Sampling
Possibility that containers of starting materials may be incorrectly labeled, steps to ensure that only the correct materials are used.
ID testing the contents of each container can provide the necessary assurance to check mislabeling of the containers and therefore mix-ups
Partial mislabelling of a delivery represents a greater potential hazard than a complete mislabelling of all the containers in a delivery

24. QUALITY CONTROL Sampling
The containers from which samples were taken for analysis, should be identified and carefully sealed after sampling.
Samplers should be adequately trained and knowledgeable in the practical aspects of sampling and should record details of any signs of contamination, deterioration or tampering in the sampling record.
Sampling tools and implements should be made of inert materials and kept scrupulously clean.

25. QUALITY CONTROL Sampling
Sampling Plan- must ensure that a representative sample of the batch is taken and consider the criticality and variability of the material, past quality history of the supplier and the quantity needed for analysis.
Sampling plans are not recommended for sampling of APIs for identification tests

26. QUALITY CONTROL Sampling Sampling Plan- Examples
The “n” plan- when the material is considered uniform and is supplied from a recognized source. n = 1 + √N
The “p” plan- when the material is uniform, is received from a recognized source and the main purpose is to test for identity. p = 0.4 √N
The “r” plan- when the material is suspected to be non-uniform and/or is received from a source that is not well known. r = 1.5 √N
N = number of containers in consignment

27. QUALITY CONTROL Testing
There should be specifications for materials and products.
Specifications and standard test methods in pharmacopoeias or suitably developed specifications or test methods
The tests to be performed should be described in the documentation on standard test methods.
Only starting materials released by the responsible officer in QC and within their shelf-life should be used in manufacturing

28. QUALITY CONTROL Retention Samples
For potential future evaluation of the quality of batches of materials and products and not for future stability testing.
Appropriately identified, representative of each batch of material/product shall be retained.
Enough to conduct at least 2 comprehensive analyses
Stored in the same immediate container-closure system in which the material/product is marketed or in one that has essentially the same characteristics.
Retained for 1 year after the expiration date of the materials/products

29. GENERAL REQUIREMENTS All incoming materials and finished products
quarantined after receipt or processing
until released for use or distribution
stored
under appropriate conditions
orderly fashion (batch segregation)
materials management
stock rotation (FEFO)
Materials for cleaning, lubrication, and pest control
Not in direct contact with product
Suitable grade, e.g. food grade

30. STARTING MATERIALS APIs & Excipients Purchasing – important operation
From approved suppliers – if possible, direct from the manufacturer
Specifications for materials
Consignment checks
Integrity of package
Seal intact
Corresponds with the purchase order
Delivery note
Supplier’s labels
Cleaned and labelled with information

31. STARTING MATERIALS Different batches in one delivery/consignment
Starting materials labelled
Name and internal code
Supplier's batch number(s) and manufacturer's on receipt
Status (e.g. quarantine, on test, etc.)
Expiry date or retest date
Role of validated computer systems
Sampled" containers identified

32. STARTING MATERIALS Use only QC released material if within shelf-life
Dispensing
Designated persons
Written procedure
Correct materials accurately weighed
Clean, properly labelled containers
Independent checks and record
Material and weight or volume
Dispensed material
Kept together and labelled

33. PACKAGING MATERIALS Primary and printed packaging materials
Purchasing, handling and control
as for starting materials
Printed packaging materials: particular attention
Stored in secure conditions with authorized access
Roll labels where possible in place of cut labels
Loose materials stored and transported in separate, closed containers - to avoid mix-ups
Issued by designated personnel
SOP for issue and returns

34. PACKAGING MATERIALS Primary and printed packaging materials
Each delivery or batch: specific reference number or identification mark
Delivery to packaging department
Check quantity, identity and conformity to packaging instructions
Outdated or obsolete material
Printed packaging materials: particular attention
Destroyed
Disposal records

35. INTERMEDIATE AND BULK PRODUCTS
Kept under appropriate conditions
If purchased as such
Handled on receipt as though these are starting materials

36. Finished products Held in quarantine until their final release
Then stored as usable stock under suitable storage conditions
Evaluation and documentation necessary for release
Product release procedure
Batch record review and related procedure

37. REJECTED MATERIALS
Should be identified and controlled under a quarantine system designed to prevent inadvertent use in manufacturing.
The Agency should be notified of decision to destroy or return to supplier.
Disposal should be in accordance with approved procedures and environmental regulations

38. REPROCESSED AND REWORKED MATERIALS
A pharmaceutical product may be reprocessed provided the subsequent meets appropriate standards, specifications & characteristics.
QC should consider additional testing of reprocessed products.
Rework of finished pharmaceutical products IS NOT PERMITTED

39. RECALLED PRODUCTS Recalled products Identified Stored separately
Secure area - access controlled
Decision taken on their fate

40. RETURNED GOODS Returned goods Destroyed unless suitable quality
SOP: decision regarding their fate (relabelling, resale, etc.)
Consider: nature of product, special storage conditions, condition, history, time elapsed since issue
Action taken to be recorded

41. REAGENTS AND CULTURE MEDIA
Records of receipt or preparation
Reagents
Preparation in accordance with SOP
Appropriately labelled:
Concentration, standardization factor, shelf-life, re-standardization due date, storage conditions
Signed and dated
Culture media
Positive and negative controls each time prepared and used
Inoculum size appropriate

42. REFERENCE STANDARDS Official/Primary Reference Standards
Use preferable whenever these exist
Only for the purpose as per monograph
Storage conditions
Reference standards prepared by the producer
Tested, released and stored in the same way as official standards
In a secure area
A responsible person
Secondary or working standards
Appropriate checks and tests at regular intervals
Standardized against official reference standards – initially and at regular intervals

43. REFERENCE STANDARDS
Reference standards labelled with information including:
Name
Batch, Lot or Control number
Date of preparation
Shelf life
Potency
Storage conditions
Stored and used in the appropriate manner

44. WASTE MATERIALS Proper and safe storage when awaiting disposal
Toxic substances and flammable materials:
In suitably designed, separate, enclosed areas as per regulation
Not to be allowed to accumulate
Collected in suitable containers for removal to collection points
Safe and sanitary disposal
Regular and frequent intervals

45. MISCELLANEOUS MATERIALS
Rodenticides, insecticides, fumigating agents
Sanitizing materials
No contamination risk to equipment, starting materials, packaging materials, in-process materials, finished products

46. CONCLUSION “Garbage in, Garbage out”
Compliance with the requirements for materials management in pharmaceutical manufacturing will lead to the good quality, safe and efficacious products

47. References NAFDAC GMP Guidelines for Pharmaceutical Products 2016
Nally, J.D. (2007). Good Manufacturing Practices for Pharmaceuticals 6th Ed. Pg
Ogbeide E. (2011) Presentation on Control of Pharmaceutical Starting Materials
WHO TRS 986 Annex 2; Good manufacturing practices for pharmaceutical products: Main principles
WHO TRS 929 (2005). Annex 4; Guidelines for sampling of pharmaceutical products and related materials
WHO. Quality Assurance of Pharmaceuticals: A compendium of guidelines and related materials. Vol. 2 2nd Ed.

48. THANK YOU

49. QUESTIONS?