GMP module 08 - Overview of Packaging Operations

Outcome of the Module:

Customers of pharmaceutical products expect products that are safe and effective. Controlled packaging operations ensure that products are safe and effective by producing finished products that are correctly identified. Product and labelling mix-ups can result in potentially serious consequences.

As such, GMP rules require that product rules be correctly identified with the correct name, ingredients, strength, and botch information. There must be no unspecified components present.

On completion of this module, you will be able to:

  • Define what is meant by mislabelling
  • State the critical GMP requirements for packaging controls
  • Describe the GMP controls for pre-printed matter
  • Identify the GMP requirements of selling up a packaging line
  • State the importance of online controls
  • Perform basic reconciliation calculations

Part I: Potential Mislabeling

Packaging mix-ups, which ore often called “mislabeling”, are of the most common causes for recoil of medicines. Particular care is required in the packaging areas to ensure that batch numbers, expiry dales, correct labels, correct cartons, and correct product information leaflets are assembled with the right product every time.

When packaging rework must occur, full packaging record documentation, complete line clearance, and oil normal controls must be used.

It is also a GMP rule that products that are mislabeled should never be “over-labelled”. This is because it is very easy to make an error in this rework, or it’s possible that the over-label maybe dislodged later, causing the product to be mislabeled once again.

A product is “mislabeled” if the labelling and packaging information does not accurately reflect the contents of the container. For example, if a label indicates that a bottle contains 100 capsules, but the bottle only contains 99 capsules, this is classified as a case of mislabeling.

A more extreme, and potentially dangerous example, is if the product was stated as being “tamper-evident”, but there is no evidence of tamper-proof seals.

It would also be mislabeled if it is not in conformance with the marketing authorization and claims. As part of product manufacture, companies must register the product’s labelling details with the regulators. If there is any deviation from these label specifications, the company is in breach of regulations.

 

Part II: Printed Materials Control

Many mislabeling incidents commence with the wrong issue of labels or other printed matter from the store.

The GMP rules clearly state that each issue of printed matter from the store must be accompanied by requisition paperwork and that there is a cross-check that labels match the documented request before issue.

The reason for this is the issue is the first point of control. It is much better to prevent incorrect labels being issued in the first place rather than finding them (or not) later on. Mislabeling can cause incorrect consumption or patient medication, which can result in serious injury or even death of patients.

There are GMP controls over how manufacturers handle printed material. Printed matter should be verified, kept separate and secure al all times. This ensures that the distributed product does not result in recall or withdrawal from the marketplace. These measures help to protect patients from taking the wrong medicines.

The term “printed matter” includes:

  • Labels for containers (rolls of labels and cut labels)
  • Package leaflets (inserts and outserts)
  • Labels for cartons or packaging
  • Printed containers (e.g. lubes)

 

Part III: Line Clearance & Setup

In a busy packing hall, there are generally many products being processed at once. Unless there are specific GMP controls in place, it is inevitable that a rogue item of printed matter will eventually end up on a different product. This may not get detected later, and could injure patients and cause a recall. Proper line segregation helps to physically separate different printed matter, much of which looks similar.

A combination of physical segregation, double line checks when new printed matter arrives, and detailed line clearances are critical GMP labelling controls.

Line clearances are used in the labelling and packaging area as another control to prevent mix-up of product, the following steps must be conducted and verified prior to the start of packaging and labelling operation:

  • Clean the area and machines,
  • Remove all previous products from the area and machines.
  • Remove all waste from the area and machines.
  • Reconcile all printed material and product from the previous batch.

Once the above steps are complete, it must be documented that the area and machines ore inspected and found to be clear of all previous product.

 

Part IV: Online Controls

On-line controls for the packaging line must be in place. Items that should be checked before, during or after operations are that:

  • Lines and equipment have been cleared of bulk material, labeling and packaging materials and documentation from previous operations, including any computer screens or systems holding information pertinent to the batch.
  • The general appearance of finished packages is satisfactory
  • The packages are complete
  • The correct product and packaging materials are being used
  • Over-printed details are correct and clearly readable
  • All line monitors, indicators, and readers are working or have worked correctly

Special attention should be paid to checking the accuracy of variable information, such as batch numbers and expiration dates to packaging components on line. Printed and embossed information on packaging materials must be clear, easy to read, and resistant to fading or erasing.

In process test equipment e.g. Leak test equipment to realize integrity of blister sealing should be on the equipment and maintenance schedule. The in process testing should be completed as appropriate to demonstrate the integrity on the blister is maintained throughout the packing order. Any failures should be documented, investigated and appropriate actions taken.

Special controls should be applied to the management of trial and experimental packing work to ensure the same level of compliance and assurance is applied for this type of work around packing, documentation and labeling compared to routine work.

 

Part V: Reconciliation

Reconciliation of printed matter is one of the key GMP packaging controls. The reconciliations indicate how many printed matter items are not accounted far.

It is well-known that incorrect calculations are common mistakes in this area, for example, assuming that any unaccounted for numbers must be rejects. While reconciliation limits should be tight around 100%, it isn’t expected that every result is exactly that number.

In a reconciliation, the quantify issued to (a known or verified count) should be compared with the sum of:

  • The quantity used for good product
  • The quantity used for rejected product
  • The quantity used for samples
  • The quantity used on documentation
  • The quantity damaged
  • The quantity returned

 

Every single measure is a count, not a calculation.

An unsatisfactory reconciliation can indicate loss of material, a gain of foreign material, a miscounting, or bad arithmetic.

Conclusion:

This module highlighted the importance for instituting packaging and labelling controls al a pharmaceutical manufacturer. GMP rules dictate that these controls are in place in order to ultimately protect the customer from mislabeling errors. Specific packaging and labelling controls govern:

  • Printed matter (e.g., control, over artwork and printers, limited access to the label store, disposal of obsolete and rejected printed mailer)
  • Validation of counting equipment
  • QC sampling
  • Line clearances
  • Continuous monitoring of critical process parameters
  • Online controls, such as:
    • – Material and label identification
    • – Count (or measure) of the filled container
    • – Seal integrity
    • – Label verifier function
    • – Coding
    • – Pack appearance
  • Reconciliation

 

Online Quiz:

Online Quiz:

  • Number of questions: 10
  • No time limit
  • Allow you save and finish at a later date
  • Allow you to go back and change your answer
  • Attempting each question is mandatory
  • Pass mark at and above 70%
  • Print results and certificates
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