6.125 Double filtration? 75 6.126 Integrity testing of filters immediately after use? 77 6.127 Are results a part of the batch protocol? 77 6.128 Optical control of each single container of ampoules, vials,
and infusions?
82
IPC
6.129 Written IPC procedures and SOPs? Particle testing of
6.130 • rooms 6.131 • primary packaging materials 6.132 • system of warning and action limits?
Microbiological monitoring of 6.133 • rooms
6.134 • personnel 6.135 • equipment
6.136 Residual O2of ampoules, infusions, and syrups?
6.137 Endotoxin testing of water and packaging materials? 6.138 Calibration of equipment? 6.139 Regular revalidation of equipment?
7 PACKAGING
Operations carried out:
• Blistering
• Foil packaging
• Filling into tablet glasses
• Effervescent packaging
• Powder filling
• Syrup/drops filling
• Ointment filling
Rooms
7.1 Suitable for the intended use? 3 7.2 • adequate size? 3 7.3 • clean? 3 7.4 Located and designed to exclude external contamination? 3.1 7.5 Appropriate level of maintenance? 3.2 7.6 Maintenance works possible without contamination risk? 3.2 7.7 Appropriate lighting and air-conditioning? 3.3 7.8 Recording of temperature and humidity?
7.9 Protection against the entry of insects or other animals?
3.4
7.10 Controlled access for authorized personnel only? 3.5 7.11 Adequate separation of the packaging lines? 3.15
Operations
Compliance 1 2 3 Remarks EU-Guide
7.13 Check list for clearance before processing a new product/new batch?
5.45
7.14 Adequate labeling of the lines (product name and code)?
5.46
7.15 Check of all materials delivered to the line (quantity, identity, conformity with order)?
5.47
7.16 Cleaning of primary packaging materials? 5.48 7.17 Immediate labeling after filling? 5.49 7.18 Careful check of all printing processes (code, and expiry date)? 5.50 7.19 Special safety measures for off-line printing? 5.51 7.20 Regular checks of all control devices (code reader, counter
etc.)?
5.52
7.21 Printings clear and durable? 5.53 7.22 Balancing of printed packaging materials and bulk? 5.56 7.23 Destruction of excessive coded packaging material after
completion of an order?
5.57
7.24 Are the finished products kept in quarantine until final release?
5.58
7.25 Appropriate storage after release? 5.60
IPC
7.26 Checks on identity of bulk and packaging materials? 5.47 Regular line checks on
7.27 • aspect of the packages 5.54a 7.28 • completeness 5.54b 7.29 • conformity of quantity and quality of materials with
packaging order
5.54c
7.30 • correct imprint 5.54d 7.31 • correct function of control devices 5.54d
Are the following IPC checks performed?
7.32 • Leaking 7.33 • Release torque of screw caps 7.34 • pH, density, drop weight, viscosity, and sedimentation
8 DOCUMENTATION
Specifications
8.1 Specifications for raw/packaging materials available? 4.10 Do they include
8.2 • internal name and code 4.11 8.3 • name of supplier and/or manufacturer? 4.11 8.4 • reference sample (printed pack. mat.)? 4.11 8.5 • sampling procedure? 4.11 8.6 • qualitative/quantitative specifications with limits? 4.11 8.7 • storage conditions? 4.11 8.8 • maximum storage period? 4.11
Goods receiving?
Compliance 1 2 3 Remarks EU-Guide
Do records receipt include
8.10 • product name on labels and delivery note? 4.20 8.11 • internal name and code? 4.20 8.12 • receiving date? 4.20 8.13 • name of supplier and/or manufacturer? 4.20 8.14 • batch number of supplier? 4.20 8.15 • total quantity and number of containers? 4.20 8.16 • allocated internal batch number? 4.20 8.17 SOPs for labeling, quarantine, and storage conditions of all
incoming goods available?
4.21
SOPs include
8.18 • authorized sampling personnel? 4.22 8.19 • methods, equipment, and quantities? 4.22 8.20 • safety measures? 4.22
Master formulae
8.21 Are master formulae for each product and batch size available? 4.3 8.22 Is the master formula approved and signed by the authorized
persons?
4.3
The master formula includes
8.23 • product name and code? 4.14a 8.24 • description of galenical form, dosage, and batch size? 4.14b 8.25 • all active ingredients with name, code, and weight? 4.14c 8.26 • all excipients used during manufacture with name, code,
and weight?
4.14c
8.27 • yields with limits? 4.14d Does the working procedure include
8.28 • the production line? 4.15a 8.29 • equipment to be used? 4.15a 8.30 • reference to methods for cleaning, assembling, and
calibration of machines?
4.15b
8.31 • detailed stepwise manufacturing prescription? 4.15c 8.32 • IPCs to be performed with limits? 4.15d 8.33 • precautions to be followed? 4.15e 8.34 Are batch records kept for each batch processed? 4.17
Do batch records include
8.35 • protocol of line clearance? 4.17 8.36 • name of the product and batch no.? 4.17a 8.37 • date and time of start and end of production? 4.17b 8.38 • name and initials of responsible workers for each step? 4.17c, d 8.39 • batch and analytical no. and actual weight of all starting
materials?
4.17e
8.40 • equipment used? 4.17f 8.41 • results of IPCs with initials of person who carries them out? 4.17g 8.42 • yields of the relevant manufacturing steps? 4.17h 8.43 • detailed notes on problems and process deviations? 4.17i
Compliance 1 2 3 Remarks EU-Guide
8.44 Records on reprocessing of batches?
Packaging instructions
8.45 Packaging instructions for each product, package size, and presentation?
4.16
Do they include
8.46 • product name? 4.16a 8.47 • description of galenical form and strength? 4.16b 8.48 • package size? 4.17c 8.49 • list of all packaging materials with code for a standard
batch size?
4.17d
8.50 • samples of printed packaging materials? 4.17e 8.51 • special precautions? 4.17f 8.52 • description of the process and equipment? 4.17g 8.53 • IPCs to be performed with sampling instruction? 4.17h 8.54 Are packaging batch records kept for each batch or
part batch?
4.18
Do the packaging batch records include
8.55 • protocol of line clearance? 4.18 8.56 • name of the product? 4.18a 8.57 • date and time when operations have been performed? 4.18b 8.58 • name of the responsible person? 4.18c 8.59 • initials of workers carrying out operations? 4.18d 8.60 • notes on identity checks and conformity with packaging
instructions?
4.18e
8.61 • results of IPCs 4.18e 8.62 • details of operations and equipment used? 4.18f 8.63 • samples of printed packaging materials with codes (MFD,
EXP, batch no. etc.)?
4.18g
8.64 • record of problems and process deviations? 4.18h 8.65 • quantities of packaging materials delivered, used,
destroyed, or returned?
4.18i
8.66 • no. of packs consumed? 4.18j
Testing
Do the written testing procedures include
8.67 • test methods? 4.23 8.68 • equipment for testing? 4.23 8.69 Tests documented? 4.23
Others
8.70 Procedures for release and rejection of materials and finished products?
4.24
8.71 Final release by authorized person? 4.24 8.72 Records about distribution of each batch? 4.25
Procedures and protocols about
Compliance 1 2 3 Remarks EU-Guide
8.74 • set up and calibration of equipment? 4.26 8.75 • maintenance, cleaning, and disinfection? 4.26 8.76 • training records? 4.26 8.77 • environmental monitoring of production areas? 4.26 8.78 • pest control? 4.26 8.79 • complaints? 4.26 8.80 • recalls? 4.26 8.81 • returned goods? 4.26 8.82 Instructions for use of manufacturing and testing
equipment?
4.27
Log books for major equipment incl. date and name of persons who performed
8.83 • validation? 4.28 8.84 • calibration? 4.28 8.85 • maintenance, cleaning, and repair works? 4.28 8.86 Chronological records of use of major equipment and
manufacturing areas?
4.29
9 QUALITY CONTROL 6
General requirements
9.1 Independent QC department available? 6.1 9.2 Head of QC well qualified and sufficiently experienced? 6.1 9.3 Qualified personnel available? 2.1 9.4 Organization charts available? 2.2 9.5 Job descriptions available? 2.2 9.6 Responsibilities clearly defined? 2.2 9.7 Continuous training programs for QC staff? 2.2 9.8 Initial job training for all employees? 2.9 9.9 Training records?
9.10 QC personnel admitted to the production rooms for sampling etc.?
QC laboratories
9.11 Suitable for the intended use? 3.26 9.12 Laboratories of adequate size? 3.26 9.13 Appropriate level of maintenance? 3.1 9.14 Adequate separation from the production area? 3.26 9.15 Controlled access of authorized personnel only? 3.5 9.16 Special laboratory to handle biological samples available? 3.29 9.17 Special laboratory to handle radioactive material available? 3.29 9.18 Separate recreation rooms for the personnel available? 3.30 9.19 Animal laboratories present? 3.33 9.20 Animal laboratories separated from other areas? 3.33 9.21 Animal laboratories equipped with a separate air-handling
system?
Compliance 1 2 3 Remarks EU-Guide