A GMP HUB - ENRICH YOURSELF

 

A GMP HUB - ENRICH YOURSELF

Product Grouping
Many companies seek a common denominator whereby similar products may be “grouped.”

Through this process, the company attempts to convert a complex situation into a manageable project.

Typically, products are first grouped according to formulation and dosage form, including considerations of potency, toxicity and solubility.

These product groupings are further subdivided
by types of equipment used in their manufacture. Further distinctions are made according to cleaning method and agent.

Cleaning Validation-The Cleaning Validation Program

 

The cleaning of the equipment should proceed in accordance with the documented standard operating procedure for cleaning.

After the cleaning has been completed, an intensive sampling of the system
may begin. (See the section on Sampling Techniques and Analytical Methods.) Attention should be given to product contact areas, intricate areas, and critical sites.

As defined previously, critical sites are those locations in which a contaminant is in danger of affecting a single dose with a high level of contamination.
The number of trials to be performed for each system is another issue which is often debated.

Most cleaning validation programs demonstrate the reproducibility of a process by three (3) consecutive trials for a single product on a single piece of equipment.

If a firm chooses to pursue the grouping philosophies for the initiation of the cleaning program, it may be part of the plan to pursue the representative products and equipment with three (3) trials each.

After completion of the trials which were "representative" of the most challenging cleaning, it may be appropriate to reduce the number of trials for subsequent products which fit within the grouping baseline.

If reducing the number of trials to be performed, great care should be taken to identify the rationale for the product grouping and to demonstrate the equivalency of new findings to the initial results.

Cleaning program- PDA

 

It is important to consider the effect that weekends, holidays and delays might have on the cleaning schedule.

It is advisable to determine the stability of material remaining on equipment for longer time
periods than in a normal manufacturing sequence.

Material typically may degrade, dehydrate or may strongly adhere to equipment after long time periods. It may be advisable to establish the stability of the product in the manufacturing equipment for the longest (i.e., worst case) holding period.

Regulatory inspectors are known to be quite interested in how the company has taken the stability and cleanability of materials into account when materials sit in equipment for long periods of time.

The product reserved in the open container should be evaluated for product degradation studies.

The validation group, user group, quality assurance group, etc. are all responsible for ensuring that the test program is an accurate reflection of actual production.

Cleaning Validation-The Cleaning Validation Program

 

Cleaning Validation

The Cleaning Validation Program

Frequently, the basis of cleaning validation programs is the establishment of a plan which describes
the overall validation approach. The rationale for any grouping philosophies utilized and the
validation program to be implemented should be identified.
After the determination has been made of which product(s) and piece(s) of equipment are to be
utilized in the validation study, the validation trials may commence. If the product is to be coated on
equipment surfaces to form a trial for cleaning validation, care must be taken that the product
coverage used for validation is appropriate to simulate the level of contamination that would be
present in an actual manufacturing situation.
Care should also be taken in the simulation of the production methods utilized. For example, a piece
of equipment that is utilized first thing in the morning may sit, contaminated with product, until the
second shift starts. Having the product "dry" on the equipment, therefore, may be the worst case.

PDA CLEANING VALIDATION

Simple Equipment Train

Complex Equipment Train

An equipment train is generally recognized as a grouping of equipment or systems which

function as a unit during the production of a product. The complexity of the "equipment

train" is based on the number of discreet pieces along the train, the number of transfer or

process steps and the ability to sample the equipment train as discreet items (e.g., closed

systems). The complexity of the cleaning validation is directly proportional to the complexity

of the equipment train.

PDA

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OPERATIONAL ISSUE

 

Operational issues such as the number of products manufactured, the use of campaigns and utilization
of equipment and the complexity of the equipment impact the design of the cleaning validation
program.

In a facility the product is manufactured using different equipment such as reactor,centrifuge,agitated nutche filter, dryer etc.

For cleaning this equipment a cleanning program shall be established based for single product or multiple product

Single Product Facility - Multiple Product Facility

The circumstances surrounding a single product facility are analogous to those for dedicated
and non-dedicated equipment.

SINGLE PRODUCT

In those instances where a facility, which might be a separate
building on a large site, produces only a single product, the validation requirements are
simplified by the elimination of cross-contamination concerns.

MULTIPLE PRODUCT

Multiple product facilities (also referred to as multi-product or multi-use facilities) clearly
represent a more difficult challenge. Procedurally, steps must be taken in a multiple product
facility to ensure that cross-contamination potentials are eliminated. Change-over of
equipment from one product to another must be carefully controlled.

After cleaningvalidation is completed, monitoring programs may be warranted which ensure that all controls
are in place and that limits established during cleaning validation are maintained.