Contamination & Cross Contamination

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An Overview of Contamination and Cross Contamination & its Prevention

What Is Contamination?

Contamination is defined as the undesired introduction of impurities of a chemical or microbial nature, or of foreign matter, into or on to a starting material or intermediate, during production, sampling, and packaging or repackaging, storage or transport.

What Is cross Contamination?

Cross contamination is defined as the Contamination of a starting material, intermediate product or finished product with another starting material, intermediate product or finished product is called cross-contamination.

Sources of Contamination

  1. People
  2. Processes
  3. Object

Micro-organisms are found by the millions in or on:

  1. The environment around us
  2. Water
  3. Raw Materials
  4. Containers and Closures
  5. People

GOLDEN RULE

“Always be on the lookout for possible contamination and guard against it”

From where Contamination come from?

Contamination is due to movement of particle and People are the major source of contamination through body regenerative processes, behavior and work habits. Particles which fall to floors with gravity or air pressure will break down into smaller ones that will move with air turbulence. The most common are less than 10 microns and invisible to the naked eye

Particles can be viable or non-viable they come in different shapes and sizes.

Likely Contaminants

As well as the last slide and more particularly:

  1. Active Pharmaceutical Ingredients (API’s)
  2. Cleaning Agents
  3. Decomposition products and materials
  4. Synthetic intermediaries
  5. Excipients
  6. Other residues

 Particulate Matter

  1. Particles are defined as bodies with definite physical boundaries in all directions; diameters ranging from 0.001 micron to 100 microns; they may be liquid or solid or both
  2. One micron equals one-millionth of a meter
  3. 25 mm = 25,400 microns
  4. Eye of a needle = 749 microns
  5. The dot of an (i) = 397 microns
  6. Depending upon light intensity/quality, most eyes cannot see below 10 microns

Particle Visibility

  1. The ability to see individual particles depends on the eye itself, the intensity, the quality of light, the background and the type of particle
  2. Particles seen on furniture or floating in rays of sunshine are 50 microns or larger
  3. The majority of invisible particles are 3 microns in diameter and smaller
  4. In ambient air, 99% of airborne particles by count are less than 1 micron

Who Generates these Particles?

  1. In short, everything generates particles
  2. 97% of these particles are not visible to us
  3. All particles represent a threat/danger to the integrity and quality of Pharmaceutical Manufacturing Facilities
  4. 80% generated by personnel
  5. 15% generated by equipment
  6. 5% generated by environment

 Motion of Particles is affected by:

  1. The Velocity field of the fluid (air!)
  2. The inertia of the particle
  3. External forces acting on the particle – gravitational, electrical, and magnetic
  4. The viscous drag (always opposite to direction of movement)
  5. Collisions with molecules, other particles or surfaces (forming agglomerates)

Cross-Contamination in Production

Prevention of cross-contamination in production

“contamination of a starting material or of a product by another material or product must be avoided. This risk of accidental cross-contamination arises from the uncontrolled release of dust, gases, vapours, sprays or organisms from materials and products in process, from residues on equipment, and from operators’ clothing. The significance of this risk varies with the type of contaminant and of product being contaminated. Amongst the most hazardous contaminants are highly sensitising materials, biological preparations containing living organisms, certain hormones, cytotoxics, and other highly active materials. Products in which contamination is likely to be most significant are those administered by injection, those given in large doses and/or over a long time”

(EU-GMP; Medicinal Products of human and vetinary use; Ch 5)

Dedicated Facilities (GMP Guide)

No Change

“GMP/GDP Inspectors Working Group has agreed that the use of dedicated facilities should normally be required when beta-lactam antibiotics are produced. In addition dedicated facilities should be

used when live pathogens are handled” (EMA/INS/GMP/809387/2009)

Going Forward

 “ for other products, manufacturers introducing a product into shared facilities should carry out an assessment of all relevant product and process characteristics to evaluate whether it is suitable

for production in shared facilities. This assessment should include input from a toxicologist. Where the product has known sensitizing potential, or is highly potent or toxic, the Supervisory Authority

should be consulted to discuss the manufacturer’s risk management measures” (EMA/INS/GMP/809387/2009)

The Opportunity to Contaminate

  1. Toxicity
  2. Quantity of active ingredient used per batch
  3. Process train used in product manufacture
  4. Level of containment and energies used in processing
  5. Proximity to other products and the use of shared equipment
  6. Opportunity to contaminate
  7. Dosing regime of the product and in particular the number of daily doses contained in a batch
  8. Frequency of the ingredients or product’s manufacture
  9. Any other products manufactured that might be contraindicated for users of the target drug

 The 5 “P’s” of Risk Assessment and Risk Management

  1. Pathogens
  2. Procedures (experimental)
  3. Personnel
  4. Protective Equipment
  5. Place

PREVENTION FOR EFFECTIVE CONTAMINATION CONTROL IN PHARMACEUTICAL FACILITIES

Contamination control has long been one of the main challenges in pharmaceutical production as nothing is a greater liability to the safety of patients-

As per FDA, GMP Regulations 1978

“There shall be separate or defined areas or such other control systems for the firm’s operations as are necessary to prevent contamination or mix-ups”

As per EMA, GMP Regulations

“In order to minimize the risk of a serious medical hazard due to cross-contamination, dedicated and self contained facilities must be available for the production of particular medicinal products”

70% to 80% of all contamination entering a room is carried in on wheels or feet (UK Department of the Environment)

  1. Contamination on unprotected floors will rise to shoulder level and above on air particle movement created by vortices
  2. Installation of a contamination control system at floor level is the most cost effective solution to the removal of the majority of contamination
  3. By removing 80% for small cost compared with the expense of trying to cope with the 20% (air handling systems, gowns, hats, gloves, physical barriers, clean, controlled, critical facility costs!!)

Preventative Measures

  1. Filters
  2. Specialist Cleaning
  3. Containment
  4. Implementation of Barrier Technology
  5. Controlling Personnel Habits
  6. Restricting foreign materials (Cardboard,Packaging, Feed etc)
  7. Contamination Control Flooring/Mats

Benefits of contamination prevention

  1. Reduced chance of Animal study failure costing considerable sums and even threatening the viability of the facility
  2. The animals have a degree of protection which can counter premature death
  3. Staff and other stakeholders see you are serious about the running of the facility and the importance of controls
  4. Increased confidence of all using the facility• Staff not needing time away through reventable illness/allergies
  5. Less time and money spent in trying to identify rogue organisms and sources of contamination

Solutions:

Dust Mats

Made from various materials  like coconut, jute and synthetic substances They can trap and hold dirt and dust but can themselves be a source of contamination They are not designed to hold particles for any, significant length of time It is possible to transfer off the dirt and dusT. They are usually cleaned by washing them

Tacky Mats

Multiple Layers of Polyethylene film coated with an acrylic adhesive Adhesive strength alone collects contamination Performance deteriorates after several footsteps/overstrikes.

Appropriate for confined spaces, with low personnel traffic volumes Low efficiency in particulate removal for smaller particle sizes of less than 10μmicrons When peeled, tens of thousands of viable and non-viable particulates are released into the environment

Cannot be recycled High costs when analyzed on an annual basis

Polymeric flooring

  1. Polymeric Composition, Optically smooth, flexible surface enabling maximum contact  between shoe and wheels
  2. High surface energy (Van de Waals forces) allows maximum collection and retention of all particulate sizes
  3. Ability to collect/retain contamination over a wide range of particle sizes, with effective removal in the 2 to 10 μmicron range
  4. Simple and regular cleaning regime guarantees effective contamination control over several years
  5. Picks up contamination over a full floor coverage
  6. Particulates removed are contained within the controlled medium thereby preventing their release into the environment
  7. Flooring can be recycled at the end of its life

Summary

Contamination can cause any number of problems, including study failure, premature animal death and illness of staff. These problems can be prevented by using and implementing an effective Risk Management policy. The amount of potential contamination will depend upon a number of factors, particularly the amount of traffic, the location and the design/construction of the Animal facility

 

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