AQL and Sampling of Packaging Materials

Standard Operating Procedure for AQL and Sampling of Packaging Materials (PM) in pharmaceuticals


Standard Operating Procedure for AQL and Sampling of Packaging Materials (PM) in pharmaceuticals

AQL and Sampling of Packaging Materials in Pharmaceuticals as per ISO 2859-1, ANSI/ASQC Z1.4, ASTM E2234, NF06-022, BS 6001, DIN 40080, and US Military Standards (MIL STD – 105E).

1. Purpose:

To provide a standard operating procedure for Sampling of Packaging Materials (PM) in pharmaceuticals.

2. Scope

The scope of this SOP is applicable for Sampling of Packaging Materials (PM) in pharmaceuticals at [company name].

3. Responsibility

Quality Control Analyst:

Sampling of Packaging Materials

Quality Control Packing Material Section Head:

Monitoring the activity and review the records

Quality Control Laboratory Head:

To ensure compliance to the procedure

4. Definitions

Not applicable

5. Procedure

• On receipt of Packing Material in the warehouse, the warehouse enters details of received material in the material management software. As soon as the Goods Inward Note (GRN) is prepared, the Laboratory Information Management System (LIMS) database for Packing Material awaiting sampling is updated.

• Daily, Quality Control laboratory personnel responsible for the packing material section (Packing Material section head) will check the list of material populated in the system displays as material to be tested.

• Packing material section head will also inquire about the priority of the manufacturing department before planning Packing Material Testing or Refer Monthly Production Planning Schedule.

• Packing material section head will allocate the material to be sampled to the Quality Control Laboratory Person responsible for sampling Packing Material (Sampler) in the LIMS.

• The sampler will log in to the LIMS and print the Packing Material sampling worksheet.

• The sampler, will reach the warehouse department and request warehouse staff to take the material to be sampled at the sampling area.

• The sampler shall verify the cleanliness of the sampling area before bringing the material inside the sampling area and starting the sampling activity.

• On arrival of Packing Material inside the sampling area, sampler will verify the material label, manufacturers’ batch number, control number/ A.R. No./ unique identification number of material (generated by material management software of the organization), and ensure that material arrived in the room is the same material that is supposed to be sampled as per sampling worksheet.

• The sampler will also ensure that the Packing Material is free from external damages. If the any damage noted, it shall be marked separately and informed to the warehouse person, packing material section head, and Quality Assurance Person.

• The sampler will verify the Packing Material using a sampling worksheet to ensure the following:

• Packing Materials shall have the label as “Quarantine” to each container with details of Material Name, Material Code, Control No./ A.R. No., Material Manufacturer’s name/ Vendor name,  Manufacturer Batch No., Manufacturing Date, Expiry Date, Quantity of material received, Number of containers received, Pack Size, Warehouse document serial number, and Total number of Containers..

• Materials shall not be accepted when the material name is not listed in the approved vendor list, if abnormality is observed during sampling, or Certificate of Analysis (CoA) not received with the material.

• The packing material section head shall verify the CoA received from the material manufacturer and compare it against the specification implemented in the organization. The packing material section head will ensure that the analysis results of the material manufacturer are within the organization’s specification limit. In case of any deviation noted, it shall be informed to the Quality Control laboratory head and Quality Assurance head to take a call on whether material shall be accepted or rejected.

• Before starting the sampling, ensure that the Sampling area environmental condition, such as Temperature, Relative Humidity, and Differential Air Pressure, is within the defined and acceptable range.

• Only one material shall be sampled at a time in Sampling Area.

• For sampling of primary packing material, ensure that Reverse Laminar Airflow (RLAF) is switched “ON” at least before [specify the time which is established through recovery study, it vary from 10 minutes to half an hour]. Record the pressure differential across the pre-filter, intermediate, and HEPA filter and ensure that readings are within the defined range. In case of any abnormality, sampling shall not be started. Instead, inform to the engineering department to rectify before beginning the sampling activity.

• Containers to be sampled shall be taken within the safe zone of RLAF. A sampling of volatile materials shall be done at solvent sampling and dispensing area.

• Before starting the sampling of material, the sampler shall follow safety precautions. Sampler needs to use required Personal Protective Equipment (PPE) during sampling. Example, Nose Mask, Hand Gloves, Safety Goggles, etc.

• Material Safety Data Sheet [MSDS] should be handy in the area as applicable.

• Before starting the sampling activity, make an entry in the logbook for sampling activity, such as material name, control number, RLAF start time (in case of primary packing material), and sampling start time.

• Once the sampling activity is completed, enter the sampling end time.

• Sampling of Secondary Packaging Materials and Tertiary Packaging Material shall be done at sampling area for respective material.

• In case of sterile packing material (Pre-sterilized packing material) satellite sample will be received along with the material. This satellite sample shall be collected. Ensure that integrity of sample container/ sample bag is maintained. In case does not provides satellite pack, any one entire container/ pack shall be collected as sample.

• In case of sterile material, verify each container for evidence of sterilization with the help of indicators available on each pack. Example, indicator for Gamma Radiation Sterilization or indicator for Ethylene Oxide (EtO) sterilization.

• Entire sterile packing material sample shall be sent to microbiologist department to carryout sterility testing. The remaining samples shall be handed over to Quality Control analyst for visual inspection check, Physical and Chemical Tests.

• Leaflets/ Patient Information Leaflet (inserts or Outserts) visual inspection to be performed in the Quality Control Laboratory.

• For Aluminum/ paper Foil,  PVC, PVdC Film, before carryout sampling discard about 1/2 meter material from role.

• If number of Joints is more than three, it shall not be accepted and information for number of joints shall be recorded in packing material sampling and observation worksheet.

• Sampling quantity to be withdrawn shall be equal from all the selected number of containers to be sampled.

• For printed packing material, multiple ups sheet/ Uncut Printed Sheet shall be provided by the packing material manufacturer with the material received and it must be approved by material manufacturer. This shall help to verify the correctness of Text matter and Appearance.

• Examples of printed packing materials are Labels, Cartons, Catch Covers, Patient Information Leaflet, Literatures, Printed Foils, etc.

• After completion of sampling, sampler shall close the container or pack to ensure material storage adequately.

• Personal Protective Equipment (PPE) such as Nose Mask, Hand Gloves and Safety Goggles, shall be used during sampling.

• Samples quantity for the sample to be collected shall be as per sampling worksheet.

• For visual inspection of packing material (spot check of packing material in warehouse during sampling), and sampling quantity is defined based on ISO 2859-1 standard. It is an international standard with equivalents in all national regulations (ANSI/ASQC Z1.4, ASTM E2234, NF06-022, BS 6001, DIN 40080) and US Military Standards (MIL STD – 105E).

• In this procedure, sample size is considered based on ISO 2859 with the following criteria:

(i) Number of packs or containers to be opened for visual inspection and sampling shall be decided as per Table 1. (General inspection level III is considered).

(ii) Acceptance and rejection criteria for visual inspection Primary Packing Material shall be decided as per Table 2. (General inspection level III is considered).

(iii) Acceptance and rejection criteria for visual inspection Secondary and Tertiary Packing Material shall be decided as per Table 3. (General inspection level II is considered).

Table 1: Number of packs or containers of Packing Material to be opened for visual inspection and sampling (General inspection level III is considered)

Sample size CodeTotal number of packs or containers receivedTotal number of packs or containers to be opened for visual inspection and collection of sample for analysis
B02 – 083
C09 – 155
D16 – 258
E26 – 5013
F51 – 9020
G91 – 15032
H151 – 28050
J281 – 50080
K501 – 1200125

Note: Sample quantity for analysis will be derived from method of analysis for respective material. Sample from each container = Total sample quantity/ Total number of packs or containers to be opened as per Table 1

 Reference: Table as per ISO 2859-1

ISO 2859 General inspection Level III

Table 2: Acceptance and rejection criteria for visual inspection of Primary Packing Material

Lot Size (Total number of items received in entire consignment)Sample size codeSample Size (Total samples collected for visual inspection)Critical AcCritical ReMajor AcMajor ReMinor AcMinor Re
2 to 8B3010101
9 to 15C5010101
16 to25D8010101
26 to 50E13010112
51 to 90F20010112
91 to 150G32011223
151 to 280H50011234
281 to 500J80012356
501 to 1,200K125013478
1,201 to 3,200L20001561011
3,201 to 10,000M31501781415
10,001 to 35,000N5000110112122
35,001 to 150,000P8000114152122
150,001 to 500,000Q12500121222122
500,001 and overR20000121222122

Note:

(i) Ac – Acceptance number, Re – Rejection number

(ii) General inspection level III is considered

(iii) Acceptance Criteria as per Normal Inspection plan – Critical at 0 %, Major at 1.0 %, and Minor at 2.5 %.

Table 3: Acceptance and rejection criteria for visual inspection of Secondary and Tertiary Packing Material

Lot Size (Total number of items received in entire consignment)Sample size codeSample Size (Total samples collected for visual inspection)Critical AcCritical ReMajor AcMajor ReMinor AcMinor Re
2 to 8A2010101
9 to 15B3010101
16 to 25C5010101
26 to 50D8010101
51 to 90E13010112
91 to 150F20010112
151 to 280G32011223
281 to 500H50011234
501 to 1,200J80012356
1,201 to 3,200K125013478
3,201 to 10,000L20001561011
10,001 to 35,000M31501781415
35,001 to 150,000N5000110112122
150,001 to 500,000P8000114152122
500,001 and overQ12500121222122

Note:

(i) Ac – Acceptance number, Re – Rejection number

(ii) General inspection level II is considered

(iii) Acceptance Criteria as per Normal Inspection plan – Critical at 0 %, Major at 1.0 %, and Minor at 2.5 %.

• Sampling person needs to record the visual inspection observation in the “Packing material sampling and observation worksheet”.

• Acceptance or rejection of packing material is decided based on the Table 2 for Primary Packing Material and Table 3 for Secondary and Tertiary Packing Material.

• Defects are classified as Critical, Major and Minor based on the following definitions:

Critical Defects: The defect in the material has highest potential to make pharmaceutical formulation unsafe with respect to product quality and patient safety.

Major Defects: The defect in the material that may impact the packaging operation and generates defects during packing operation and have potential for multiple customer complaints but does not have patient safety risk.

Minor Defects: The defect in the material that may impact on product appearance and have potential for few customer complaints, but may not have impact on product quality and patient safety.

• In case the samples are received as satellite pack for testing, and quantity of sample is insufficient to carryout AQL, AQL can be done on intact sample pack/ container through the transparent bag without opening the pack. After completion of AQL, pack shall be return to warehouse.

• AQL inspection to be done while new lot of material received. During re-test AQL inspection shall not be carried out.

• Once the sampling is completed, sampler shall affix “Under Test” Labels to all the packs. Under test label shall have details Material Name, Material Code, A.R. No. / Control No., Manufacturer name, Manufacturer Batch No., Manufacturing Date, Expiry Date, quantity received, Number of pack/ container, Pack Size, Sampled By, Sampled on, Sampled Pack Nos.

• Number of “Under Test” label generated shall be total number of packs + One. One additional label shall be generated to affix with the analytical report.

• Details of sampling and visual inspection details shall be recorded in the “Packing material sampling and observation worksheet”.

• Sampler shall carry required tools such as polybag, Scissors, and Rubber Band etc.

• When sampling is planned, QC sampler will inform to the warehouse person to locate the material and take it to the sampling area.

•Identify the number of packs to be open for AQL and sampling as per Table 1.

• Ensure that the packs are clean. If require, packs shall be cleaned from external surface.

• Note the quantity of material to be sampled. The sample quantity is calculated using method of analysis and it is listed in the “List Packing Material Sample Quantity”.

• Number of pack to be sampled shall be derived using Table 2 and Table 3 for primary packing material, and secondary and tertiary packing material respectively.

• Record the AQL results and quantity of material sampled in the “Packing material sampling and observation worksheet”.

• Example of deriving packs to be opened and samples to be collected from number of containers.

Total number of packs for HDPE containers received (Primary Packing Material20 Packs
Total number of HDP bottles received20000 Bottles
Each pack consist of number of bottles1000 Bottles
Based on the Table 1, Sample Size Code is D. Hence, total number of packs or containers to be opened for visual inspection and collection of sample for analysis8 Packs
Total sample quantity required for analysis to carryout full testing as per method of analysis are200 bottles
Sample to be collected from each pack (from 8 packs) are 200 divided by 825 bottles from each container
Packs to be considered for sampling will be representative of entire lot receivedPack 1, 3, 6, 9, [10 or 11], 12, 15, 18, and 20
Based on the Table 2, Sample Size Code is N. Hence, total number of bottles to be collected for AQL/ Visual inspection are500
Sample to be collected from each pack [from 8 packs (Pack 1, 3, 6, 9, [10 or 11], 12, 15, 18, and 20)] are62 from 4 packs and 63 from 4 packs container
Critical defect Acceptance0
Critical defect Rejection1
Major defect Acceptance10
Major defect Rejection11
Minor defect Acceptance21
Minor defect Rejection22

• The container which is sampled will be affixed with label “Sampled” for identification purpose.

• “Under Test” label shall be affixed at inner core in case of aluminum foils, PVC or PCV/PVdC Films, or roll labels.

• Once the sampling is completed, request to warehouse person to transfer the material to its respective location.

• Sampler shall send the sample to Quality Control laboratory for analysis and details shall be recorded in packing material inward register.

• Sample shall be stored at location as per required storage condition.

6. Frequency

For all new incoming packing material and during retest of material. 

7. Formats

7.1 Packing material sampling and observation worksheet

DescriptionObservation/ Compliance
Material Name 
Material Code 
A.R. No./ Control No. 
Material Manufacturer 
manufacturing Batch No. 
Manufacturing Date 
Expiry Date 
Quantity received 
Number of  Packs received 
Pack Size 
Type of Packaging 
Quantity Sampled 
Sampled Pack No. 
Foreign Matter/ Contamination 
Packaging Condition/ Damage 
Sampling Room environmental condition: Differential Pressure l Readings, Temperature and Relative Humidity 
Manufacturer’s CoA compliance with organizations specification 
Material is pre-sterilized (Yes/ No) 
Mode of sterilization (Gamma/ ETO/ Other specify __________) 
Sterilization indicator availability on each container (Yes/ No) 
Indicator color observed [Specify standard color for each type of sterilization for sampler’s understanding and observation] 
Number of Joints (Applicable for foil and film) 
Total number of packs received 
Total number of packing material quantity received 
Each pack consist of number of packing material 
Sample Size Code as per Table 1 for total number of packs or containers to be opened for visual inspection and collection of sample for analysis 
Total sample quantity required for analysis to carryout full testing as per method of analysis are 
Sample to be collected from each pack 
Pack Nos. to be considered for sampling 
Sample Size Code as per Table 2 (Primary Packing Material) or Table 3  (Secondary and Tertiary Packing Material) for total number of packing material to be collected for AQL/ Visual inspection are 
Sample to be collected from each pack for visual inspection/ AQL are 
Critical defect Acceptance 
Critical defect Rejection 
Critical defect observed 
Major defect Acceptance 
Major defect Rejection 
Major defect observed 
Minor defect Acceptance 
Minor defect Rejection 
Minor defect observed 
Visual inspection/ AQL Complies/ Does Not Comply 
Storage condition 
Material sampled and AQL done By 
Checked by 


7.2 Packing material sample inward register (Content of logbook)

Sr. No.

Sampling Date

Material Name

A.R. No./ Control No.

Quantity Received

Quantity Sampled

Manufacturer name

Material inward entry made by

Date of material approved/ rejected

Analyst name

Analyst sign

Leftover sample quantity after analysis

Leftover sample quantity destroyed by

7.3 List Packing Material Sample Quantity (Content of logbook)

Sr. No.

Name of Material

Quantity to be sampled for newly received material

Quantities to be sampled during sampling for re-test

7.4 Packing Material defect classification for AQL/ Visual inspection

Material NamePrinted Carton
Critical defectsMix-ups, Missing text matter or color, Missing embossing, Wet cartons, Dirty cartons
Major defectsLocking defects, Improper pasting, Stuck cartons, Smudging of printing matter, Shifting of text matters
Minor defectsImproper creasing or folding, Shade/ color variation
Material NamePlain Carton
Critical defectsMix-ups, Wet cartons, Dirty cartons
Major defectsLocking defects, Improper pasting, Stuck cartons
Minor defectsImproper creasing or folding, Shade/ color variation
Material NameCatch Covers
Critical defectsMix-ups, Missing text matter or color, Missing embossing, Wet Catch Covers, Dirty Catch Covers
Major defectsLocking defects, Improper pasting, Stuck Catch Covers, Smudging of printing matter, Shifting of text matters
Minor defectsImproper creasing or folding, Shade/ color variation
Material NameLabels
Critical defectsMix-ups, Missing text matter or color, Wet Labels, Dirty Labels
Major defectsImproper pasting, Stuck Labels, Smudging of printing matter, Shifting of text matters, Improper Cutting, Torn Labels
Minor defectsShade/ color variation
Material NameInserts, Outserts, Leaflets, PIL, Booklet
Critical defectsMix-ups, Missing text matter or color, Wet Labels, Dirty material
Major defectsImproper Cutting, Smudging of printing matter, Torn Leaflets, Shifting of text Matters
Minor defectsShade/ color variation
Material NameHDPE Drum / Fiber Drum
Critical defectsExtraneous dust or particulate matter, Hole, Cut
Major defectsDamaged container, Molding Defects, De-shape
Minor defectsShade/ color variation
Material NamePlain Alu Foil, PVC Film, PVC Acler, PVC-PVdC Film, Alu Ali Foil, Peelable foil
Critical defectsMix-ups, Damaged core
Major defectsLoose winding, Telescopic winding, Stain
Minor defectsShade/ color variation, Joints more than accepted numbers
Material NamePrinted aluminum foil/ Peelable paper foil
Critical defectsMix-ups, Damaged core, text matter or color missing, Damaged core
Major defectsLoose winding, Telescopic winding, Stain
Minor defectsShade/ color variation, Joints more than accepted numbers
Material NameStretch Film
Critical defectsNot applicable
Major defectsWet or dirty
Minor defectsDamaged core, Loose winding
Material NameCotton, Polyester, Rayon
Critical defectsWet or dirty, undesirable odor
Major defectsStain, Foreign particles
Minor defectsNot applicable
Material NameContainer/ bottle
Critical defectsMix-ups, extraneous dust, foreign/ particulate matter Hole or cut
Major defectsDamaged Container, Molding defects, De-shape
Minor defectsShade/ color variation, Stain
Material NameHDPE bottle, LDPE bottle, Container, Closure
Critical defectsMixing of container other than mentioned product Extraneous dust or particulate matter Hole or cut
Major defectsDamaged container Moldings defects (De shape)
Minor defectsColor Shade Variation
Material NameRubber Stoppers, Stopper Plunger
Critical defectsDamage, cut, Mix-ups
Major defectsMolding defects, De-shape
Minor defectsNot applicable
Material NameBOPP tape, Glue tape
Critical defectsNot applicable
Major defectsShade variation
Minor defectsDamaged core
Material NamePrinted BOPP tape, Glue tape
Critical defectsNot applicable
Major defectsShade variation
Minor defectsDamaged core
Material NameShipper, Corrugated box, Grey board box, Thermocole Box
Critical defectsWet, Dirty
Major defectsStains, Rusted stales, Rust marks, Spots, Damaged, Closing defects, Improper box formation, Improper folding
Minor defectsShade variation
Material NameAir bubble bag
Critical defectsNot applicable
Major defectsHole, Cut, Wet, Dirty
Minor defectsDamaged bag, Missing air bubbles
Material NameAluminum Bag, Polyethylene bag , Heat shrink cover
Critical defectsHole, Cut, Wet, Dirty
Major defectsImproper sealing, Damaged
Minor defectsNot applicable
Material NameStickers
Critical defectsNot applicable
Major defectsHole, Cut, Wet, Dirty
Minor defectsImproper pasting ability
Material NameSilica gel bag, Silica gel sachet, Silica gel canister, Molecular sieve sachet, Oxygen absorber canister
Critical defectsHole, Cut, Wet, Dirty, Leak
Major defectsDamaged, Improper sealing
Minor defectsNot applicable
Material NamePlastic seal (Plain, Printed)
Critical defectsMix-up
Major defectsInappropriate sealing ability
Minor defectsShade variation
Material NameVials, Pre Filled Syringe, LDPE bottle
Critical defectsExtraneous dust or particulate matter, Wet, Dirty
Major defectsCracks, Air bubble, Molding defects, De-shape, Damaged
Minor defectsNot applicable
Material NameHDPE/LDPE Nozzles(Eye Dropper)
Critical defectsMix-up, Extraneous dust or particulate matter, Wet, Dirty, Hole, Cut
Major defectsDamaged nozzles, Molding defects, De-shape
Minor defectsShade variation
Material NameAluminum Flip Off Seal
Critical defectsNot applicable
Major defectsMolding defects, De-shape, Damaged
Minor defectsShade variation
Material NamePlastic Tray
Critical defectsWet, Dirty
Major defectsMolding defects, De-shape, Damaged, Cracks
Minor defectsShade variation
Material NameSterile needles in pack
Critical defectsOpen Pack
Major defectsNot applicable
Minor defectsNot applicable
Material NameSterile syringe in pack
Critical defectsOpen pack, Hole, Cut
Major defectsDamage, Molding defect, De-shape
Minor defectsNot applicable
Material NamePlunger Rod
Critical defectsMix-up
Major defectsMolding defect, De-shape
Minor defectsNot applicable
Material NameWooden Pallet
Critical defectsWet, Dirty
Major defectsDamaged, Stains, Rusted nails, Rust marks, Dust, Any other contamination
Minor defectsNot applicable
Material NamePre-filled Syringe safety guard
Critical defectsBroken, Cracked
Major defectsImproper spring
Minor defectsSpots, Dust
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